T.O.

Lecture 1: Introductory Histology

Lecture 2: Getting the Histology Picture

Lecture 3: Histology of the Alimentary System I

Lecture 4: Histology of the Alimentary System II

Lecture 5: Histology of the Alimentary System III

Lecture 6: Histology of the Alimentary System IV (Pancreas)

Lecture 7: Renal System I

Lecture 8: Renal System II

Lecture 9: Endocrine Glands I

Lecture 10: Endocrine Glands II

Lecture 11: Sensory Systems I (Vision)

Lecture 12: Sensory Systems II (Ocular Lens Pathology)

Lecture 13: Male Reproduction I

Lecture 14: Male Reproduction II

Lecture 15: Sensory Systems III (Touch, Pain, Taste, & Smell)

Lecture 16: Sensory Systems IV (Hearing & Equilibrium)

Lecture 17: Female Reproductive System I (Ovaries)

Lecture 18: Female Reproductive System II (Uterine tube, Mammary gland)

Lecture 19: Female Reproductive System III (Uterus)

Lecture 20: Female Reproductive System IV (Cervix and Vagina)

Lecture 21: Fertilization and Pre-implantation Embryo Development

Lecture 22: Fertilization and Pre-implantation Embryo Development

Lecture 1: Introductory Histology

● Histogenesis = the embryonic development of specialized forms of cells/tissues/organs

from unspecialized tissue.

Fertilization to Implantation
● Within first week of development, an egg is released (ovulation) and makes contact with
a spermatozoa as it moves along the oviduct.
● Begins to divide from a single cell → 2, 4, 8 → morula → blastocyst which will
embed on the uterine epithelial surface.
● Blastocyst = ball of Trophoblast cells with an inner cell mass consisting of an Epiblast
and Hypoblast.
○ Trophoblast cells invade the uterine wall and become the supporting placenta.

Blastocyst during implantation

● Epiblast cells produce amniotic fluid contributing to the amniotic cavity.
● The cavity grows and envelopes the developing embryo.
● The amniotic fluid protects the embryo throughout the gestation period.

Gastrulation in the Blastocyst

● The epiblast layer → forms the Endoderm.
○ In time, the epiblast layer goes on to form the Ectoderm too.
● Unspecialized germ layers → forms the Mesoderm.

Histogenesis
● Tissues = cells of the same type that are structurally and functionally linked.
● Organs = different tissues that are structurally and functionally linked.

Tissues
● Tissues are made up of an ordered arrangement of cells that can form distinctive
patterns. Specific arrangements allow them to cooperatively perform a specific function.
 ● 4 basic tissue types:
○ Epithelial tissue: lines body surfaces and cavities (morphology)
○ Connective tissue: holds everything together (morphology)
○ Muscular tissue: specialized contractile cells (functional)
○ Neural tissue: transmits information (functional)

Epithelium
● Basic properties:
○ Covers the inner + outer surfaces of the body.
○ Attached to a basement membrane.
○ Has an apical-basal polarity.
○ Avascular (no blood).
○ Connected via junctions.
○ Has the ability to shed (surface) and restore (basal stem cells).
○ Has barrier functions: separates outside from inside, can prevent or facilitate the
passage of same substances.

Epithelium classifications (relation to function)

1. Simple epithelium
a. Monolayer; one cell layer thick.
b. Has receptors; can transport molecules.
2. Stratified epithelium
a. Multilayers; 2 or more cell layers thick.
b. Provides protection.
c. The shape of the cell on the surface determines its classification.
3. Pseudostratified epithelium
a. “False” multilayering.
b. Multiple cell shapes.
c. All sit on a basement membrane but not all reach the surface.
d. Provides protection + secretion.
4. Transitional stratified epithelium
a. Can change cell layer numbers.
b. Multiple cell shapes.
c. Provides protection + ability to stretch/distend.
- Can be Squamous / Cuboidal / Columnar.

Specialized simple squamous epithelium

1. Endothelium = lines all blood vessels
2. Mesothelium = lines closed internal body cavities and surfaces of organs (e.g., thoracic
cavity)
● Serosa:
○ Made up of mesothelium overlying a layer of connective tissue
○ Covers outer surface of organs (visceral; inner body cavity) and body cavities
(parietal)
 ● Mucosa:
○ Made up of epithelium cells overlying a layer of connective tissue.
○ Covers inner surface of organs and vessels.

Apical surface modifications on epithelium

Plane of section and tissue orientation

● Cutting sections:
○ 1. Transverse/Cross-section
○ 2. Longitudinal

Magnification and Resolution

Light Microscopy Electron Microscopy

Resolving power 0.2μm 3nm

Max magnification 2000x 500,000x

Section thickness 1μm 0.025nm

Cellular ultrastructure
● Rough Endoplasmic Reticulum (rER)
○ Structure: cisterna covered with ribosomes.
○ Function: protein synthesis.
● Smooth Endoplasmic Reticulum (sER)
○ Structure: cisterna and glycogens.
○ Function: metabolism, detoxification, isolate Ca2+.
● Golgi Apparatus
○ Structure: cisterna form crescent shape with vesicles budding off.
○ Function: sorting and packaging proteins.

Respiratory tract (functional systems)

● Structure-function
○ Air conduction; transports air
○ Air filtration; traps air
 ○ Air conditioning; humidifies air
○ Respiration; gas exchange
● 4 layers within its walls:
○ 1. Mucosa (epithelium)
○ 2. Mucosa (lamina propria)
○ 3. Submucosa (glands, muscles, cartilage)
○ 4. Adventitia

Respiratory epithelium: Trachea (structure-function)

● Mucosa: ciliated pseudostratified columnar epithelium with goblet cells + lamina propria.
○ Contains elastic fibers, collagen, fibroblasts, blood vessels, inflammatory cells,
and lymphatic tissue.
● Submucosa: loose connective tissue
○ Contains sero-mucous glands, hyaline cartilage, and smooth muscle (trachealis
muscle).
● Mucous (secreted by goblet cells + glands) traps particles, humidifier air, and provides
fluid cilia movement.
○ Cilia movement is coordinated to propel trapped particles towards the pharynx
(where it is expelled/swallowed).
■ Impaired cilia → recurrent respiratory infections.

Respiratory tract: conducting

● Bronchus: cartilage plates
● Bronchiole: no cartilage, glands
○ Terminal bronchiole: simple cuboidal cells
○ Respiratory bronchiole: breaks in wall, reduced muscle
● Alveolar wall: air-blood barrier / gas exchange
○ Alveolar sac/duct
○ Alveoli: squamous epithelium, no muscle

Lecture 2: Getting the Histology Picture

Commonly used histology stains
● Structures with negative charge (anionic) stain more readily with basic dyes
(basophilic).
● Structures with positive charge (cationic) stain more readily with acidic dyes
(acidophilic).

1. Polychromatic stains (Basic & Acidic dyes)

○ Hematoxylin-Eosin
i. Dark purple
ii. Stains cytoplasm + strongly stains nuclei
iii. Focuses on nuclei
○ Hematoxylin-Eosin-Saffron (HES)
i. Typical affinity to Collagen/Elastin
ii. Focuses on protein
2. Extracellular matrix stains (Trichrome)
○ Trichrome Blue
○ Trichrome Green
○ Mallory Trichrome
3. Dedicated Polychromatic stains (Polysaccharides, Elastin, Myelin)
○ Periodic Acid-Schiff
i. Highlights Elastin rather than Collagen
ii. Dark red/purple
○ Orcein
i. Highlights Elastin fibers sitting b/w the epithelial cells and other cell types.
○ Luxol Fast Blue
 i. Stains Myelin tissue and protein components present b/w nervous tissue.
4. Orthochromatic + Metachromatic dyes (‘May-Grunwald-Giemsa’)
○ Does not stain with an affinity to DNA (e.g., red blood cells).
○ Orthochromatic dyes do not change colour on binding to a target. Metachromatic
dyes are the opposite.
5. Monochromatic dyes (basic dyes)
○ Aniline Blue → Osteons
○ Toluidine Blue → Individual skeletal muscle cells
6. Impregnation stains (Neural inclusions, Calcium)
○ Typically combined with polychromatic stains.
○ Focuses on something that we know is readily present in a certain
tissue (e.g., nerve tissue → neurons).
○ ‘Cajal’ dye
i. Stains Reticulum fibers (components that make up neural cells) with dark
lines.
○ ‘von Kossa’ dye
i. Focusses on Calcium (e.g., build-up of bone tissue stains as dark-brown).
ii. Gives an idea of bone formation / degradation.

Microscope Histology
● Optical image → Digital image → Input digital image → Digital image storage
→ Digital image output.

Uneven illumination
● Light is captured at different angles and places in your field of view.
● Light bulb → typical uneven illumination
● LED → gives a more homogenous eld of illumination

Colour aberrations
● If lens is oversimplied, the blue light rays will meet closer to the lens. The
opposite will happen for red light (projected much more further down the
optical axis) → distortion.
● E.g., blue-ish shadow surrounding histology sections → “colour aberrations”.
● How to correct colour aberrations = combine an additional piece of lens with
a high density with a lens of low density → all the light rays will meet at one
point.
○ Corrected lens: “apochromatic”
● Digital image correction: Filter Gaussian Blur

Illumination and Resolving Power

● Acceptance Angle Objective: 2 points you want to image captured by the objective when
light hits the sample.
○ When the 2 points are smaller (< 220-240nm), lights will be scattered
around in various directions → image will NOT be captured by the
 objective.
● D = ⋌ / 2n x sinθ
○ D = distance / resolution
○ ⋌ = wavelength of white light
○ n = refractive index
○ sinθ = sin of angle of acceptive angle of objective

Calibrating Magnification
● Objective size estimation =
● Drawing magnification =

Quantifying Histology Information

● Histomorphometry: the quantitative measurement of the form of tissues
and/or cells (and their parts) → gives an objective way / scientic values to
use in statistical analysis for shape in particular.
○ Surface area
○ Diameter
○ Cell/Tissue boundary (perimeter)
○ Length of structure
■ All these individual values are represented in a form factor
■ Perfect circle = form factor 0 / irregular shape = form factor 1

Lecture 3: Histology of the Alimentary System I

Alimentary tract: oral cavity

● Alimentary mucosa = surface across which most substances enter the body
○ Consists of epithelium with an underlying connective tissue (lamina propria) and
a muscularis mucosa (muscle layer).
 ● Functions:
○ Secretion → enzymes, mucous, hormones, antibodies
○ Absorption → breakdown products from digestion in the intestines
(carbohydrates, lipids, proteins, etc.)
○ Barrier & immunological protection → stops the entry of toxic
substances and pathogens
● Oral cavity = mouth and its structures
○ Vestibule: space b/w lips, cheeks, and teeth
○ Tongue → for eating and speaking
○ Teeth and supporting structures
○ Salivary glands → secretion of saliva
○ Tonsils → part of lymphatic tissue
● Epithelial cells, neutrophils, lymphocytes and saliva produced in the glands all
maintain the general/overall health for the oral cavity → prevent infections.

Alimentary tract: 4 general layers

1. Mucosa
a. Epithelium
b. Lamina propria
c. Muscularis mucosa
2. Submucosa
a. Dense irregular connective tissue
b. Glands, nerves, blood vessels
3. Muscularis externa (further down in alimentary tract)
4. Serosa (mesothelial lining) or Adventitia (connective tissue around the organ attaching to
another organ)

Mucosa types in the oral cavity

● 3 types:
○ 1. Masticatory mucosa → hard palate, gingiva (gums)
■ In locations with the potential of experiencing lots of abrasions
○ 2. Lining mucosa → lips, cheeks, soft palate, oor of mouth
○ 3. Specialized mucosa → associated with sensation of taste (tongue)

Masticatory mucosa
1. High abrasive stress (e.g., hard palate, gums)
○ Keratinized (orthokeratinized: fully keratinized) stratified squamous epithelium
○ Deep proprial papillae
○ Dense connective tissue in lamina propria
2. Moderate masticatory stress (further towards the back of the mouth)
○ Parakeratinized (intermediate b/w ortho and non-keratinized)

Hard palate
● Contains ortho and parakeratinized epithelial cells
 ○ Parakeratinized cells have pyknotic (highly condensed) nuclei
● Deep proprial papillae protects from frictional + shearing stress.
● In parts (e.g., palatine raphe) adheres to bone and no submucosa

Lining mucosa
● Little mechanical stress (e.g., lips, cheeks, soft palate)
○ Non-keratinized stratified squamous epithelium
○ Shallow proprial papillae and less dense (loose) connective tissue

Soft palate
● Generally not keratinized
Lip
● Lining mucosa is generally non-keratinized, but a portion (b/w moist inner surface and
facial skin) is keratinized.
● Blood vessels and nerve endings are responsible for the lip’s red colour and sensitivity.
○ Surface epithelium is thin → vascularity of connective tissue allows
colour to show through.
● Connective tissue papillae deeply penetrates into the base of the stratified squamous
epithelium.
Specialized mucosa
● Unique to the tongue.
● Lingual papillae and associated taste buds cover the surface of the tongue (e.g., dorsal
surface).
● Circumvallate papillae are found on the V-shaped depression (sulcus terminalis), which
separates the tongue into anterior ⅔ and posterior ⅓.
● Lingual tonsil: lymphatic tissue in lamina propria.
● Lingual muscles (striated): allows flexibility and precision of movement important for
swallowing and speech.
○ Tongue has ~3 bundles of skeletal muscle all positioned perpendicularly with
each other.
● Complex nerve supply.
● 4 types of papillae:
○ Filiform (most common)
○ Fungiform (taste buds)
○ Foliate (taste buds)
○ Circumvallate (taste buds)

Filiform papillae
● Smallest and most abundant – no taste buds.
● Projections of connective tissue covered with keratinized stratified squamous epithelium.
● Mechanical role: tips point backwards and aid in the movement of bolus to back of
mouth.
Fungiform papillae
● Mushroom shaped scattered amongst filiform papillae.
● Numerous near tongue tip.
● Taste buds present.

Foliate papillae
● Parallel low ridges separated by mucosal clefts on lateral edges of tongue.
● Taste buds present.
● Glands empty into clefts via ducts.

Circumvallate papillae
 ● Largest dome-shaped 8-12 in humans.
● Taste buds present on sides.
● Ducts of lingual salivary glands empty serous secretion at base to flush material away
(as a response to changing stimuli).
● Surrounding clefts.

Taste buds
1. Neuroepithelial (sensory) cells – most numerous with microvilli
2. Support cells – microvilli
3. Basal cells – smallest cells, near basal lamina, STEM cells
- Taste buds are mostly present in the tongue. Also present in the soft palate, epiglottis,
and posterior wall of the pharynx.

Taste
 ● Taste = chemical sensation where the substance consumed react with receptor on
neuroepithelial cells.
○ Taste has various “taste maps”; certain areas of the tongue will be
more sensitive to specic stimuli (e.g., tip of tongue → sweetness).
○ Stimulation of taste receptors → increases intracellular enzymes that
activate membrane ion channels to increase intracellular Ca2+⁺. This
releases neurotransmitter which generate nerve impulse.
● 5 stimuli:
○ Sweet
○ Salty
○ Bitter
○ Sour
○ Umami (taste of certain amino acids - e.g., glutamate, aspartate).
● Ability to sense specific tastes is genetically determined (e.g., supertasters).

Teeth
● Consist of 3 specialized layers of tissues:
○ 1. Enamel (crown of the tooth)
○ 2. Dentin
○ 3. Cementum (cements the tooth to the periodontal ligament)
● Dental pulp = connective tissue bounded by dentin, highly vascularized with nerve
supply.

1. Enamel: hard, thin translucent acellular mineralized material that covers the crown.
a. Hardest substance in the body – calcium hydroxyapatite
b. Formed from epithelial cells; ameloblasts
c. Composed of rods
d. Once tooth emerges from gums during development, ameloblasts never form
again.
 e. Maintenance by secretions of salivary glands (becomes decalcified by acid
producing bacteria).
2. Dentin: calcified material that is the most abundant tissue.
a. Tubular structure
b. Secreted by odontoblasts – epithelial layer (columnar)
i. Contains rER, golgi due to synthesis of lots of protein.
ii. Also secretes predentin
c. As dentin is deposited, the layer of odontoblasts retreat leaving behind
odontoblast processes embedded in the dentin = dentin tubules.
d. Rhythmic growth of dentin forms growth lines marking development events (e.g.,
birth).
e. Predentin = matrix close to odontoblast not mineralized yet.
3. Cementum: thin pale yellowish bone-like calcified layer that covers root of tooth.
a. Soft and permeable and removed by abrasion
b. Secreted by cementocytes that sit in the lacunae (similar to osteocytes)
c. Processes extend into canaliculi but these do not communicate with each other
as they do in bone
d. Avascular
e. Embedded to socket by collagen fibers (Sharpeys fibers) = periodontal ligament
which allows slight movement.
Salivary glands
● 3 major salivary glands (paired structures):
○ 1. Parotid glands = serous; lots of adipose tissue
○ 2. Submandibular gland = mixed (mostly serious in humans)
○ 3. Sublingual = mixed glands (most mucous in humans)
● Minor salivary glands (in submucosa):
○ Buccal = in the mouth
○ Labial = in the lip
○ Lingual = on the tongue
○ Palatine = at the back of the mouth
● Salivary glands develop from oral cavity epithelium as a solid cord of cells that enters
mesenchyme.
● Become highly branched with bulbous ends.
● Degeneration of innermost cells of cords leads to canalization. Cords become ducts and
the bulbous ends become secretory acini.
● Acinus is blind sac composed of secretory cells (acinar cells):
○ 1. Serous cells (spherical) = protein secreting
○ 2. Mucous (tubular) = mucin
○ 3. Mixed (seromucous)
■ Cap of serous cells = serous demilunes (half moon) artifact of fixation due
to expansion of mucous displacing serous cells.
● Glands are surrounded by capsule of connective tissue from which septa divide portions
of gland into lobules.
○ Blood vessels and excretory ducts are found in the septa.
● Myoepithelial cells are contractile and move secretory products to excretory duct – lies
b/w plasma membrane of epithelial secretory cells and basal lamina.

● Mucin produced by mucous cells are stored in mucinogen vesicles (appear pale in light
microscopy because they become empty at fixation).
○ Nucleus flattened at base of cell.
○ Carbohydrates are added to proteins to produce glycoprotein of mucin.
● Protein produced by serous cells contain lots of rER, ribosomes, golgi and numerous
secretory vesicles near apical surface.
○ Indicative of high amounts of protein synthesis.

● Submandibular gland – mixed acini, both serous and mucous acini.

Ducts
● Secretory ducts – simple cuboidal epithelium
● Intercalated ducts (smallest) – b/w secretory acinus and larger duct
● Intralobular (striated) ducts – infoldings of the basal plasma membrane of columnar cells
cause striations.
○ Striations – morphological specialization associated with resorption of
electrolytes and fluid.
● Excretory ducts – largest that empty into oral cavity (can be stratified or
pseudostratified).

Saliva
● Saliva – combined secretions of all glands for protective + digestive function.
○ Contains water, proteins, glycoprotein (enzymes + antibodies), and electrolytes.
○ High bicarbonate.

Lecture 4: Histology of the Alimentary System II

Mucosa
● Epithelium = barrier allowing absorptive function of digested nutrients, water, electrolytes
into blood/lymph.
○ Secretory function of mucosa provides lubrication while delivering enzymes,
hormones, and antibodies into lumen.
● Lamina propria = contains glands, blood vessels (via fenestrated endothelial cells) to
allow transport of absorbed substances and immune cells.
● Muscularis mucosa = defines the boundary b/w mucosa and submucosa.
○ Smooth muscle cells that produce movement of mucosa to facilitate absorption
and secretion.

Esophagus
 ● Non-keratinized stratified squamous epithelium.
● Muscularis mucosa present (thick in upper portion to aid in swallowing).
● Mucous secreting glands (helps with lubrication) present in:
○ Upper and lower parts of esophagus within lamina propria.
○ Submucosa
● Muscularis externa present in:
○ Striated in upper ⅓
○ Mixed in middle
○ Smooth in lower ⅓

● Middle ⅓ of esophagus: both smooth (fusiform shape) and skeletal muscle

(red/cylindrical shape with multiple peripherally-located nuclei – for swallowing).
● Submucosal glands:
○ Mucous secretion helps in lubrication for passage of food.
○ Provides protection to the epithelium – b/c acidic contents from the stomach (via
reflux at gastroesophageal junction) can damage the epithelium in the
esophagus.

Gastroesophageal (esophagogastric) junction

● Mucosal changes:
○ 1. Stratied squamous epithelium (protective) → simple columnar
epithelium (secretory)
○ 2. Lamina propria with loose connective tissue → lamina propria
dominated by glandular tissue.

Esophagus → ← Stomach
Stomach
● Contains glands (glandular)
● 3 regions of stomach:
○ 1. Cardia
○ 2. Fundus
○ 3. Pylorus
● Mucosa is characterized by:
○ 1. Simple columnar epithelium containing mucous secreting cells (for protecting
epithelium from the acidic environments).
○ 2. Epithelium is indented by cavities (gastric pits that reach the muscularis
mucosa).
○ 3. Mucosal glands (secretes mucinogen, digestive enzymes, and HCl into bottom
of pits).
● Rugae = longitudinal submucosal folds that allow stomach to distant when full.
● Mammillated areas = grooves that increase surface area for secretion.
● Stomach function → secretion (NOT absorption).

● Cell types:
○ 1. Mucous secreting cells = epithelium.
○ 2. Parietal cells = secrete HCl.
■ Round cells with central nucleus.
○ 3. Chief cells = secrete pepsinogen into stomach which concerts pepsin to break
down protein.
■ Pale cytoplasm with nucleus at base of cell.
○ 4. Stem cells = contain in mitotic figures and found in gastric pits.
○ 5. Enteroendocrine cells = release hormones (e.g., gastrin).

Surface mucous secreting cells

● Possess a large cap of mucinogen granules.
● Thick and viscous mucous that protects epithelium from HCl.
● Mucous secreting “neck cells” are found down the necks of the gastric pits (but do NOT
contain as much mucous and are smaller/shorter cells).
Parietal cells (oxyntic)
● Secretes HCl
● Intrinsic factor = glycoprotein that complexes with vitamin B12 → important
for absorption in the small intestines.
● Intracellular canalicular system in connection with lumen of gland where HCl is produced
for digestion.
● Many mitochondria present for high levels of energy needed for acid secretion
● Long life-span (150-200 days)
● Found in neck region and upper part of gastric pits.

Chief cells
● Protein secreting cells.
● Lots of rER in basal cytoplasm → basophilic staining cell.
● Apical cytoplasm is eosinophilic b/c zymogen granules (enzyme precursors).
● Secretes pepsinogen.
● In contact with gastric juice pepsinogen / pepsin
○ Pepsinogen is hydrolyzed (broken down into smaller peptides) into pepsin.
● Several glands open into one gastric pit.
● Found at base of gastric pits.
Mucous neck cells
● Mucous neck cells = STEM cells that give rise to the surface mucous cells.
○ Mitotic activity occurs at the isthmus.
● Neck cells migrate up to differentiate into surface mucous (life span 3-5 days).
● Neck cells also migrate down to differentiate into: parietal, chief, and enteroendocrine
cells (life span 1yr).

Enteroendocrine cells
● Release hormones (Gastrin) into parietal cells. Gastrin stimulates parietal cells to form
acid.
● Enteroendocrine cells do NOT secrete their products into the pit; they have hormone
secretions that go into the lamina propria, blood vessels, and nearby cells (parietal
cells).
● Dicult to identify b/c they do not really take up the H&E stain at all → clear-
looking.
● Also referred to as “Argentaffin” cells.

Stomach cell types identifications

Cardiac stomach (anterior part of stomach)
● Mainly have mucous secreting cells + few parietal cells.
● Have shallow gastric pits (depth is less than half thickness of mucosa).

Fundic stomach (main portion of stomach)

 ● Contains many parietal cells (towards the top).
● Also chief cells and enteroendocrine cells (towards the bottom).
● Length of gastric pits are NOT used as definitive features in fundic stomach.
○ Instead, gastric glands are characteristics for fundic stomach.

Pyloric stomach (posterior part of stomach)

● Mainly mucous secreting cells + few parietal cells.
● Very deep gastric pits (more than half thickness of mucosa).

Glands of the stomach

Small intestine
● Greatest amount of digestion occurs here.
 ● Mixes chyme with enzymes + secretions from liver (bile) and pancreas.
● Absorbs most products of digestion.
● Produces hormones
● Has “Plicae circulares” = circular folds of mucosa to slow down passage for mixing.
1. Muscularis externa (Serosa):
○ Longitudinal muscle
○ Circular muscle
2. Mucosa (Submucosa → Lumen):
○ Muscularis mucosa
○ Lamina propria
○ Epithelium
● 3 parts:
○ Duodenum
○ Jejunum
○ Ileum

Small intestine – Villi

● Villi = finger-like projections of mucosa (extends up to 1.5mm into lumen).
● Contains core of lamina propria – fibroblasts, smooth muscle cells, lymphocytes, plasma
cells, eosinophils, macrophages, fenestrated capillaries.
○ Specialized for absorption.
● Also contains arterioles, capillary network, venule, and lacteal.

Small intestine – simple columnar epithelium

1. Enterocytes (absorptive cells) – columnar with microvilli.
2. Goblet cells (unicellular mucin-secreting cells) – secrete mucous.
 3. Enteroendocrine cells
○ Found at base of absorptive cells.
○ Produce hormones to stomach
○ Contain paracrine hormones, somatostatin, and histamine (all local effects).
4. Paneth cells – contain refractile secretory granules that contain antibacterial lysozymes
that dissolve bacteria.
○ Found at the lower half of crypts (along with stem cells).
5. M cells (microfold cells)
○ Have microfolds instead of microvilli.
○ Modified enterocytes that cover lymphatic nodules.
○ Conveys micro-organisms and macromolecules to Peyer’s patches.

Enterocytes
● Basally-located nucleus
● Brush border of microvilli.
● Tight junctions allowing selective retention of substances absorbed by the enterocytes.
● Na+ pumps in lateral membranes responsible for transport of substances
from cell → intracellular space → connective tissue below containing
capillaries and lacteal.

Microvilli
● Apical surface specialization of plasma membrane.
● Each cell has several thousands.
● Visible on light microscopy ONLY as “brush border”.
● Each microvillus has a core of actin microfilaments that insert into the terminal web.
○ Contraction of the terminal web → microvilli spreads increasing space
to expose more surface area for absorption.
● Plasma membrane of microvilli plays important role in digestion + absorption.
● Has anchored digestive enzymes.

Lipid absorption
● Lipid droplets are processed in vesicles of sER.
● Lipoprotein particles enter the lacteal b/c they are too large to enter capillaries.
 ○ Ends up in the liver for processing.

Goblet cells
● Water soluble mucinogen is lost during histology preparation + apical part of cell appears
empty. Basal portion is basophilic due to rER, ribosomes, nucleus, etc.
● Characteristic shape with apical granules and narrow basal stem (shaped like a wine
goblet).
● Secretory function: secretes mucous onto the epithelial surface (important for protection
against incoming acidic foods from stomach).

Crypts of Lieberkuhn
● = Intestinal glands found at base of villi.
○ Extends to muscularis mucosa via extension of epithelium that form intestinal
glands.
● Brunner’s glands in submucosa open into crypts.
○ In the duodenum.
○ Empties into the Crypts of Lieberkuhn.

Villus – crypt
● The villus crypt architecture = barrier + nutrient uptake.
● Cell replacement at villus tips (3-5 days) is fueled by stem cells in crypt.
● Crypt provide protective niche for stem line. Paneth cells protect stem cell line.
● Genetic signaling cascades determine cell fates.
Duodenum
● Duodenum contains Brunner’s glands in submucosa (defining feature of duodenum) that
drain their alkaline secretions into base of crypts of Lieberkuhn.
 ○ Secretion has high pH alkaline glycoproteins and bicarbonate ions that neutralize
the acidic (low pH) chime coming through from the stomach.

Jejunum
● = Principle site of absorption of nutrients in small intestines.
● No Brunner’s glands in submucosa.

Ileum
● Same histological features as jejunum. However, more lymphatic tissue is in the lamina
propria that form accumulations called “Peyer’s patches”.

GALT (gut associated lymphatic tissue)

● Prominent in lamina propria in villi.
● Immunological barrier throughout alimentary system.
● Lymphatic tissue and M cells are present with antigens in the epithelial intracellular
 spaces.
● Lymphocytes process the antigens and migrate to lymphatic nodules in lamina propria
where they undergo activation – secreting antibodies from plasma cells.

Microbiota
● = Collection of microorganisms that populate the body (bacteria, archaea, viruses, fungi,
protozoa, helminths) – particularly in the gastrointestinal tract.
● Pathogens encounter microbiota before they reach epithelium – both beneficial and
detrimental interactions occur.
○ Influences epithelial permeability (by degrading tight junction proteins)
○ Influences activity of enteroendocrine cells
○ Affect immune cells by increasing immune activity.

Lecture 5: Histology of the Alimentary System III

Large intestine
● 4 parts:
○ 1. Caecum
○ 2. Colon
○ 3. Rectum
○ 4. Anal canal
● Primary function: resorption of electrolytes
and water + elimination of undigested
food/waste.
● Smooth mucosa and no more villi (b/c no
absorption).
● Crypts of Lieberkuhn still present.
● Mucosal epithelium contains same cell
types as small intestines EXCEPT for
Paneth cells.
○ Simple columnar epithelium,
enterocytes, goblet cells
● Goblet cells become more numerous
towards the rectum (secretion of lots of
mucous to lubricate bowel and facilitate
elimination of waste).

Large intestine – mucous

● The intestinal epithelium is a barrier to antigens (role of mucous layer).
● Colon has a mucous layer as first line of defense formed by goblet cells.
● Inner layer of mucous formed of packed mucin sheets (impermeable to bacteria). Outer
 layer is less organized and harbours microbiota.
● Microbial molecules trigger secretion of mucous by a specific class of goblet cells that
are positioned at crypt entrance = “sentinel / guardian goblet cells”.
○ These signal to goblet cells in upper crypt to produce more mucous to expel any
bacteria.

Teniae coli
● = Possess 3 thick bands of the outer longitudinal layer of muscularis externa.
● On external surface sacculations, haustra coli are visible b/w teniae coli.

Large intestine – lamina propria

● In the large intestine, the lamina propria has a thick layer of collagen b/w
basal lamina of epithelium and capillaries → participates in water and
electrolyte transport from intercellular epithelium to vasculature.
● Well developed lymphatic tissue that extends into submucosa (this reflects the presence
of microorganisms and noxious end products present in lumen).
● No lymphatic vessels present.
● Presence of pericryptal fibroblast sheath = a population of replicating fibroblasts that
may differentiate into macrophages (for additional role in immune response).

Recto-anal junction

Liver overview
● Primary function = uptake storage and distribution of nutrients and vitamins (from blood).
● Primary EXOCRINE function = production of bile → aids in digestion +
absorption of lipid.
 ● Also produces plasma proteins = albumins, lipoproteins, glycoproteins, blood clotting
agents, non-immune globulins.
● Maintains blood glucose level.
● Stores and converts vitamins (A, D, K) and iron
○ Vitamin D is inactive until it is hydroxylated in the liver and sent to kidneys.
● Degrades drugs and toxins.
● Produces phospholipids and cholesterol.
● ENDOCRINE functions = modifying structure and function of hormones (e.g., thyroxine,
growth hormone, insulin, and glucagon).

Liver – blood supply

● Unique dual blood supply:
○ 75% deoxygenated blood from hepatic portal vein.
○ 25% oxygenated blood from hepatic artery.
● Venous deoxygenated blood supply is from the intestine, pancreas, spleen via the
hepatic portal vein.
○ Then drains through the liver into a central vein or hepatic venule →
runs into the inferior vena cava → to the heart.
● The liver is the first organ to receive metabolized substances – nutrients and toxins.
○ Also receives blood cells, breakdown products (from spleen), and endocrine
secretions (from pancreas).
● The 2 blood sources mix just before entering the liver at the “hilum” (porta hepatis).
○ Cells of the liver never receive fully oxygenated blood.

Liver – tissue and functional unit

● Major functional tissue:
○ Tissue mass of liver = parenchyma.
○ Characteristic cells = hepatocytes (arranged
into organized plates).
○ Sinusoids = specialized vascular capillaries b/w
hepatocytes.
○ Fibrous capsule of Glisson = connective tissue
around structures.
● Functional unit of liver = lobule (hexagonal shape).
○ Stacks of plates of hepatocytes separated by
sinusoids.
○ Terminal hepatic venule (central vein) in the
middle.
○ Portal triad at the edges of lobules.
● Blood comes in through the portal artery/vein →
mixes → runs through the sinusoids to the central vein.
● Portal triad (inter-lobular vessels) = portal vein, hepatic artery, bile duct, and 4 lymphatic
vessels.
○ Centripetal blood ow: portal triad → central vein (via sinusoids).
 ○ Centrifugal bile ow: hepatocytes → out towards portal triad (into bile
duct).

● Hepatic sinusoids are lined by:

○ 1. Endothelial cells with fenestrae/gaps b/w cells (has discontinuous basal lamina
to allow for solutes absorbed from the blood to pass through).
○ 2. Kupffer cells (macrophages derived from monocytes) that breakdown
damaged red blood cells
● Blood sinusoid drains → central vein → sublobular vein
○ Converge to form hepatic vein that empties into inferior vena cava of the heart.

Perisinusoidal space
● Perisinusoidal space (i.e., space of Disse) = site of exchange between blood and
hepatocytes.
○ Hepatocytes have microvilli (to increase surface area for exchange).
 ● Proteins + lipoproteins (synthesized by hepatocytes) are transferred through
perisinusoidal space into blood.
● Lymph = plasma remaining in perisinusoidal space drains in same direction (one way) as
bile to lymph vessels in space (space of mall).

Liver – exocrine function

● Primary function of liver = production of bile to aid in digestion + absorption of lipid.
● Hepatocytes have a large round central nucleus (often binucleate).
○ Contains organelles:
■ Abundant rER, sER, free ribosomes, and golgi
complexes
■ Abundant mitochondria
■ Abundant peroxisomes
● Peroxisomes (mitochondria-like) site of
O2 used for detoxification of
substances.
■ Glycogen deposits
■ Lipid droplets
■ Lysosomes and lipofuscin pigment
■ Numerous microvilli on surface (for uptake of
soluble nutrients from blood)
Canaliculi
● Hepatocytes produce and secrete bile into the canaliculi (small canals on surface of
hepatocyte that form ring around cell).
○ Sealed by zonulae occludens (tight junctions) to prevent leakage.
 ● Bile will be produced in the cytoplasm of the hepatocytes → shunted into the
canal.

Hepatic stellate cells

● Hepatic stellate cell (Ito cell) = found in perisinusoidal space next to hepatocytes.
○ Stores vitamin A in lipid droplets → transferred to the retina and is
involved in formation of rhodopsin (visual pigment of rods and cones in
retina).
● Cytoplasm also contains contractile elements (e.g., smooth muscle and actin – to
increase vascular resistance in sinusoids).
● Remodels extracellular matrix during recovery from liver damage.

Liver – Bile
● Canaliculi join to form intrahepatic ductules (“canals of Hering”) via cuboidal epithelial
cells called “Cholangiocytes”.
● Bile empties into interlobular bile ducts between the lobules at the portal triad.
● Composition of bile: water, phospholipids, bile salts, bile pigments, and electrolytes.
● Bile bind to metabolites in the intestine to aid in digestion and absorption (mainly of
lipids).
● Bile contains conjugated and degraded wastes that return to intestine for disposal (e.g.,
Bilirubin end product of hemoglobin degradation).

Biliary tree
● Bile leaves the liver via common hepatic duct → cystic duct → gallbladder (to
become concentrated).
● Biliary tree = system of vessels (increasing in diameter) which bile ows
through from hepatocytes → gallbladder → intestine.

Liver regeneration
● The only organ that can regenerate in its entirety.
○ Each cell type has the capacity to regenerate (no presence of stem cells).
○ Cholangiocytes can differentiate into hepatocytes.
● Liver has (mostly) its own circulating immune system – lymphocytes stay in sinusoids
and travel into tissue when needed.
○ Also has unusually high levels of Natural Killer T cells.

Gallbladder
● Stores and concentrates bile up to 10x.
● Pear-shaped blind pouch.
● Delivers bile → duodenum via common bile duct (under hormonal control
from enteroendocrine cells of small intestine that induces smooth muscle of
gallbladder to contract).
● Gallbladder mucosa = simple columnar epithelial cells with microvilli.
○ Lamina propria is highly vascular and cellular (lymphocytes + plasma cells)
 ○ NO muscularis mucosa
○ NO submucosa
● Muscularis = randomly oriented bundles of smooth muscle with lots of collagen and
elastin. NO clear inner circular or outer longitudinal layers.
● Adventitia = connective tissue with adipose cells connecting gallbladder to liver.
● Serosa = thin layer of connective tissue and layer of mesothelium. NOT attached to liver.

● When gallbladder is empty, mucosa becomes folded

○ Extensions of these folds down into the muscularis = “Rokitansky-Aschoff”
sinuses.
● Coupled transport of salt and water make up the concentration of bile.
● Osmotic gradients are caused by the active transport of salts into intercellular spaces of
epithelial cells.
○ Osmotic gradient → water moves into intercellular space from lumen
(dilute bile), causing hydrostatic pressure (solvent drag) and forcing
water into lamina propria and vessels.

Lecture 6: Histology of the Alimentary System IV (Pancreas)

Pancreas overview
● = a gland with 2 key functions:
○ 1. Production of (digestive) enzymes to breakdown food (exocrine function).
○ 2. Production of hormones to aid digestion (endocrine function).
● Pancreatic juices travel down the pancreatic duct.
○ Pancreatic juices are secreted in an inactivated state → must mix with
bile from gallbladder and enter the duodenum (via Papilla of Vater) to
become active.
Pancreas – structure
 ● Stroma
○ Connective tissue capsule: surrounds the outside of the organ.
○ Connective tissue septa: divides pancreas into lobules
■ Blood vessels, nerves, and ducts present.
○ Reticular fibers: supports the pancreatic parenchyma.
● Parenchyma – the lobules themselves contain the exo-endocrine cells:
○ Exocrine cells: acini and ductal systems
○ Endocrine cells: islets of Langerhans

Pancreatic Parenchyma
● Divided into lobules containing:
○ Acinar cells (exocrine) that secrete enzymes for digestion.
○ Pancreatic islet cells / islet of Langerhans (endocrine) that produce glucagon
and insulin for the blood.
● Accessory ducts (3 major types) → pancreatic duct.

Exocrine pancreatic cells

● Tightly packed clusters of branched tubuloacinar glands (lobules).
● Consist of pyramidal secretory epithelial cells that surround a lumen (acini).
● Apical tight junctions on the luminal surface.
● Basal lamina supports the basal surface.
● Centrobasal (center-bottom) nucleus.

Acinar cells
● Prominent endoplasmic reticulum and golgi complexes –
basophilic.
● Cytoplasm rich in secretory granules (Zymogen granule)
towards apical surface facing into the lumen.
○ Zymogen granule = location of digestive enzyme
secretions.
○ Stain red with H&E.
○ Contain digestive enzymes (activated upon entry to
duodenum).
● Centroacinar cells = spindle shaped extensions of intercalated
ducts into each acinus (that is clear staining).

Zymogen granules
● Contain digestive enzymes within acinar cells.
○ E.g., proteases, lipases, glycosidases, nucleases… (19 identified total) all break
down different elements of ingested foods.
○ Secreted as inactive precursors – if secreted in active form, they would damage
the acini cells and pancreas as they travel.
Pancreatic Ducts
● (1) Intercalated → (2) Intralobular → (3) Interlobular → (4) Main pancreatic
duct.
○ As ducts increase in size, lining changes from: (1) Cuboidal → (2) Low
columnar → (3) Columnar epithelium.

INTRAlobular vs. INTERlobular ducts

● INTRAlobular ducts:
○ Not striated
○ Cuboidal epithelium
○ WITHIN the lobules
● INTERlobular ducts:
○ More columnar epithelium
○ Eosinophilic striations in the basal cytoplasm (appears pink-ish colour)
○ BETWEEN lobules within connective tissue septae
Endocrine pancreatic cells
● Secretes hormones and regulates blood glucose levels.
● Islets of Langerhans
○ Endocrine part of glandular tissue.
○ Abundant in tail of pancreas.
○ Surrounded by reticular fibres.
○ Paler staining in H&E.

Islets of Langerhans (endocrine)

● Highly vascular (fenestrated capillaries).
○ The hormones that these cells secrete get taken up into the blood and
transported around the body.
● Contains 3 major cell types:
○ 1. Alpha cells (15-20%; at the periphery)
■ Secretes glucagon (increases blood glucose).
○ 2. Beta cells (70%; at the center)
■ Secretes insulin (decreases blood glucose).
○ 3. Delta cells (10%)
■ Secretes somatostatin (inhibits secretion of insulin and glucagon).
○ 4. Other cells (1%)
■ Secretes PP cells (pancreatic polypeptide) – regulates the secretion
activities of the pancreas.
 ■ E-cells (ghrelin) – modulates appetite and plays a role in the
development/secretory activities of pancreas.

Beta cells (β-cells)

● Most prolific in the Islet of Langerhans.
● Produces and secretes a lot of insulin-containing granules as a response to high
glucose.
○ A lot of them get degraded and only a small proportion gets secreted into the
blood.
● The granules are smaller than in Alpha cells and more dense than in Delta cells.
● All Beta cells make contact with capillaries – for targeted secretion of the insulin
granules towards them.
○ Efficient at secreting insulin/other hormones into the blood.

Recep – Exocrine Pancreas

Recep – Endocrine Pancreas

Pancreatic diseases
● Diabetes
○ Type 1 – autoimmune destruction of beta cells.
○ Type 2 – reduced secretion of insulin by beta cells.
● Pancreatitis
○ Abnormal activation of digestive enzymes in pancreas → inammation.
○ Damage of acinar cells – necrosis.
○ Acinar degranulation (acute)
 ○ Interlobular fibrosis (chronic)

Pancreatic cancer
● “Pancreatic ductal adenocarcinoma (PDAC)” – arise mainly from ductal epithelial cells of
exocrine pancreas (acinar cells).
● Cells harbour mutations
○ Activation of oncogenes (KRAS)
○ Inactivation of tumour suppressor genes (p53)
○ Leads to aggressive cell proliferation
○ Poor dierentiation of cells → lots of stroma

Lecture 7: Renal System I

Kidney – function
● Main function: homeostasis – maintain the stability of the extracellular fluid volume,
electrolyte composition and osmolarity (solute concentration).
○ Homeostasis is important for metabolic functions to occur properly.
● The kidney affects a number of other systems / processes in the body.
● Homeostatic functions:
1. H2O balance → to prevent osmotic uxes in/out of cells
(swelling/shrinking).
2. Plasma volumes → regulates arterial blood pressure.
3. Acid-Base balance via H+ (hydron) and HCO3- (bicarbonate) urinary output.
4. Ion concentrations and balance (Na+, K+, Ca+, H+, Mg+, HCO3-, PO4(3-), Cl-).
5. Excretion of waste products of metabolism (urea from proteins + bilirubin from
hemoglobin).
6. Endocrine functions – Erythropoietin (EPO) production
○ EPO stimulates red blood cell production, division, and growth.
○ EPO produces Renin (via RAS system) → important for regulating
blood pressure/volume.
7. Activation of Vitamin D
○ A steroid hormone that is produced in the body after sun exposure.
○ Not active until it becomes fully metabolized in the Kidney →
Liver.
8. Excretion of drugs + non-nutritive materials.

Kidney
● Consists of an outer region (Cortex) and an inner region (Medulla)
● The Ureter takes urine down to the urinary bladder.
● Serosa made up of simple squamous mesothelium lining.
● Renal corpuscles (round structures) that indicate the Kidney cortex.
 ● Sequence of Kidneys:
○ (1) Nephron → (2) Collecting Duct → (3) Minor Calyx → (4) Major Calyx
→ (5) Renal Pelvis → (6) Ureter → (7) Urinary Bladder → (8) Urethra /
out

Nephrons
● The functional units of the kidney.
● Contains:
○ Renal Corpuscle (at the cortex region)
■ Accompanied by Glomerulus (ball of capillaries)
○ Convoluted Tubules (lined by simple cuboidal epithelium)
■ Proximal → Loop of Henle → Distal
○ Loop of Henle (at the medulla region)
○ Collecting Duct
● The straight portions of the tubule that sit parallel to each other = Medullary rays (lined
by simple cuboidal epithelium)
○ This parallel arrangement is important for the pressure gradient b/w the different
parts of the tubules.
Renal corpuscle
● Consists of:
1. Glomerulus (capillary loops) – sits within Bowman’s capsule.
○ Consists of capillaries, mesangial cells, and podocytes.
2. Bowman’s Capsule (double-layered epithelial cup).
○ Consists of 1. Visceral layer (podocytes) and 2. Parietal layer (squamous
epithelium) = double-layered.
3. Urinary space (true space).
○ All urinary filtrate empties out into the proximal convoluted tubule to be
processed.

Podocytes
● Morphology – cell body + cytoplasmic/foot processes.
○ Acts as the visceral Bowman’s capsule.
Mesangial cells
● Located between the capillaries and podocytes.
● Mesangial cells are CONTRACTILE (can affect blood flow) and PHAGOCYTIC (to clear
away debris).
● If a nephron sustains a lot of damage, mesangial cells will replace the dead/damaged
tissue with collagen (non-functional tissue) – not ideal.

Tubules in cortex
● Proximal and Distal Convoluted Tubules – simple cuboidal epithelium.
○ Located in the cortex; extends down into the medulla.
 ○ Runs parallel with each other + loop of Henle (Medullary rays).

Medullary rays

Proximal convoluted tubules

● Initial and major site of reabsorption (we don’t want everything in the ltrate
to go out → low blood volume).
● Lined by cuboidal epithelial cells.
● Specific modifications for absorption function:
1. Microvilli (on apical surface) – specialized for absorption; high SA.
2. Junctional complex (on lateral surface).
3. Plicae (on lateral surface).
4. Basal striations (at base of the cell).
5. Basal infoldings (at the basal plasma membrane) – increases SA of cell.
6. Numerous mitochondria (in basal region) – high energy demands for absorption.
● Its lumen appears ‘shaggy’ b/c the microvilli on the apical surfaces.

Distal convoluted tubules

● Only ⅓ as long as Proximal convoluted tubules.
● Lined by cuboidal epithelial cells.
● Specific modifications for absorption function:
1. Very few short microvilli – not as much absorption happening here compared to
Proximal convoluted tubules.
2. Junctional complex (on lateral surface).
3. Plicae (on lateral surface).
4. Basal striations.
5. Numerous mitochondria (in basal region).
 ● Shorter tubules in Distal than Proximal = less profiles of distal convoluted tubules.

Collecting ducts
● A lot larger than proximal/distal convoluted tubules – taller epithelium lining.
○ Simple cuboidal or columnar epithelium.

Connective tissue in the kidney

● Very minimal connective tissue surrounding the nephrons, tubules, and blood vessels.
○ B/c the kidney is a very functional organ → mostly functional tissue
(parenchyma).

Lecture 8: Renal System II

Filtration apparatus
● Located in the renal corpuscle.
1. Glomerular capillaries
○ Fenestrated endothelium
○ Diaphragm is absent.
2. Glomerular basement membrane (GBM)
○ Much thicker than normal.
3. Visceral layer of Bowman’s Capsule
○ Made up of podocyte cells.
○ Podocyte extend cytoplasmic processes around capillaries (i.e., pedicels or foot
processes).
4. Slit diaphragm
○ Extends between the pedicels/foot processes.
● Blood comes in through the AFFERENT arteriole into the capillary bed and
then leaves through the EFFERENT arteriole → maintains high blood pressure
across the capillary bed.
● Molecules that are >4nm, >70 kDa in mass, and negatively charged are excluded from
the ultrafiltrate.
● High hydrostatic pressure forces small molecules (water, glucose, amino acids, urea,
 ions) through the filter.
● All via passive diffusion (NO active transport).

Juxtaglomerular apparatus
 1. Macula densa cells
2. Juxtaglomerular cells (modified smooth muscles)
3. Extraglomerular mesangial cells (special mesangial cells that sit just outside the
glomerulus)
● Endocrine function = regulates blood volume/composition by stimulating the
release of Renin via the renin-angiotensin-aldosterone (RAS) system →
regulates blood pressure.

Macula densa cells

● Located in the wall of Distal convoluted tubule.
● Tall, narrow cells with crowded nuclei.
● Function:
○ Senses the sodium (Na+) levels in the excretory.
○ If levels are too high/low, macula densa cells release prostaglandins to
set o a paracrine reaction on juxtaglomerular cells → releases renin
straight into the lumen of the arteriole / bloodstream → modies blood
pressure.
Juxtaglomerular cells
● Modified smooth muscle cells in afferent arteriole wall.
● Has spherical nuclei and cytoplasmic granules that contain Renin.
● Endocrine function = releases Renin into bloodstream in response to macula densa
cells.

Extraglomerular mesangial cells

● Stain / appears pale – difficult to differentiate from other podocytes and mesangial cells.
● Located outside the glomerulus near the arterioles.
● Part of the juxtaglomerular apparatus.
● Phagocytic just like regular mesangial cells.
● (Postulated) functions = secretion of proteins that stimulate red blood cell production (via
Erythropoietin) and angiogenesis (formation of new blood vessels).
Urinary bladder
● Lined by transitional epithelium and underlying lamina propria.
○ At the base → cuboidal cells
○ In the middle → columnar cells
○ On the surface → dome-shaped cells (can be binucleated)
● The shape of the epithelia change shape (flatten/stretch) when the urinary bladder is full
(vs. relaxed).
● Muscular beneath contains lots of smooth muscle in the wall → allows
contraction of the muscle for urinating (under autonomic control).
Ureter
● Same features and the Urinary bladder – transitional epithelium, lamina propria, smooth
muscle.
○ BUT adipose is present underneath the smooth muscle.

Urethra
● Males:
○ 20cm long
○ 3 different classifications:
■ Prostatic urethra (transitional epithelium)
■ Membranous urethra (transitional → pseudostratied columnar)
■ Penile urethra (pseudostratied columnar → stratied squamous
at distal end).
● Females:
○ 3-5cm long
 ○ Initially transitional → stratied/pseudostratied columnar in middle →
stratied squamous at distal end.

Lecture 9: Endocrine Glands I

Endocrine glands
● Endocrine system is composed of endocrine glands that produce various hormone
secretions to regulate the activity of various cells/tissues/organs.
● Endocrine glands = made up of groups (“cords”) of secretory cells of epithelial origin
(epithelioid) that rest on a basement membrane.
○ All embedded within a supportive framework of connective tissue containing
extensive vascular + lymphatic vessels.
● Hormone = a biological substance acting on specific target cells by binding to specific
hormone receptors.
○ A hormone can belong to 3 possible classes (depending on their chemical
structure):
■ 1. Peptides (e.g., insulin, GH, ACTH)
● Long chains that readily dissolve when released into the
bloodstream. Do not require any transport proteins.
■ 2. Steroids (e.g., gonadal, adrenocortical)
● Derived from cholesterol (lipid component) and require binding
protein.
■ 3. Amino acids (e.g., thyroid)
● Secreted directly into bloodstream.
● Endocrine glands do NOT contain ducts (unlike exocrine) – hormones are secreted (by
parenchymal cells) into the interstitial space. Here they reach their target cells via the
extracellular connective tissue and/or vascular system.
○ Essentially… they directly secrete into blood vessels or adjacent areas to where
they are embedded.

Hormone control mechanisms

● 3 basic types of control mechanisms:
1. Endocrine control = secretion into the bloodstream (where it is then transported
to its target cells).
2. Paracrine control = secretion into the connective tissue space (where they
target the adjacent cells that express specific receptors).
3. Autocrine control = secretion that acts on the secretory cell itself.

Hormone receptors
● Receptors are exposed on the surface (or within its cytoplasm or nucleus) of the target
cell.
● 2 groups of hormone receptors:
 1. Cell surface receptors = interacts with peptide hormones or catecholamines
that are unable to penetrate the cell membrane.
2. Intracellular receptors = localized within the cell (mainly within the nucleus) and
interact with steroids and thyroid hormones that can easily penetrate both
plasma and nuclear membranes (membrane-soluble proteins).

Regulation of hormone secretion and feedback mechanism

● Feedback mechanisms from the target organ usually control hormonal production.
● Feedback occurs when the action of a hormone has an effect on the hormone-secreting
cell.
● 2 types of feedback mechanisms:
○ 1. Negative feedback = occurs when the response decreases the original
stimulus (common).
○ 2. Positive feedback = occurs when the response increases the original stimulus
(rare).
● The hypothalamus and pituitary gland act together to regulate endocrine/neuroendocrine
control of other endocrine tissues via feedback mechanisms.

The Hypothalamus
● Most endocrine functions are coordinated by the hypothalamus.
● The hypothalamus also regulates pituitary gland activity through:
○ 1. Hypothalamo-hypophyseal tract (of nerve fibers) = links the paraventricular
and supraoptic nuclei of the hypothalamus to the posterior lobe of the pituitary.
○ 2. Hypothalamo-hypophyseal portal system = carries the neuroendocrine
secretions of the hypothalamus directly to the anterior lobe of the pituitary.

The Pituitary Gland or Hypophysis

● Small gland located at the base of the brain that functions as the “master gland” of the
endocrine system – it directs signals to the thyroid, adrenal, glands, ovaries, testes, etc.
to produce their respective hormones.
○ Adenohypophysis = Anterior Pituitary = Pars Distalis
○ Neurohypophysis = Posterior Pituitary = Pars Nervosa
■ Considered an extension of the CNS (not classified as a gland itself).
Blood supply
● The Hypothalamo-hypophyseal portal system provides the crucial link b/w the
hypothalamus and the pituitary gland.
● 2 sets of vessels that supply blood to the pituitary gland:
○ 1. Superior hypophyseal arteries = supplies the parts tuberalis, median
eminence, and infundibulum.
■ Arises from the internal carotid arteries and posterior communicating
artery of the Circle of Willis.
■ Give rise to fenestrated and sinusoidal capillaries (the primary capillary
plexus) that drain into the “hypophyseal portal veins” that gives rise to a
second fenestrated and sinusoidal capillary network (the secondary
capillary plexus).
■ The system of vessels sends the neuroendocrine secretions from
the median eminence + infundibulum → Anterior pituitary.
○ 2. Inferior hypophyseal arteries = primarily supplies the Posterior pituitary.
■ Arises solely from the internal carotid arteries.
● (Most of the anterior lobe has no direct arterial supply).

Adenohypophysis (anterior)
● Subdivided into 3 areas:
○ 1. Pars distalis (anterior pituitary)
■ Consists of cords of glandular epithelial cells within a rich network of large
fenestrated capillaries.
○ 2. Pars intermedia
■ Arises from vestigial cells leftover from Rathkespouch.
○ 3. Pars tuberalis
■ Part of the adenohypophysis that wraps around the infundibular stalk.
■
● The cells of pars distalis secrete hormones into the surrounding capillaries to act
downstream on their target cells (in response to hormones released by the
hypothalamus).
Adenohypophysis (anterior) – histology
● 3 distinct cell types:
1. Acidophils (eosinophils) – A
2. Basophils – B
3. Chromophobes – C

(Cap = capillaries)

Adenohypophysis (anterior) – hormone secretion

● 5 distinct cell types among the acidophils and basophils (distinguished functionally by
the hormones they secrete, size, and arrangement of stored granules).
○ Acidophils (2):
■ 1. Somatotrophs (e.g., growth hormone (GH))
■ 2. Mammotrophs (e.g., prolactin)
○ Basophils (3)
■ 3. Corticotrophs (e.g., adrenocorticotropic hormone (ACTH))
■ 4. Gonadotrophs (e.g., follicle-stimulating hormone (FSH) + luteinizing
hormone (LH))
■ 5. Thryotrophs (e.g., thyroid-stimulating hormone (TSH))
Neurohypophysis (posterior)
 ● The supraoptic and paraventricular nuclei synthesize oxytocin (OXY) and
antidiuretic hormone (ADH) → transported down hypothalamo-hypophyseal
tract → stored in neurosecretory granules (called Herring bodies).
● The hypothalamus conducts the signals that control the release of the stored
hormones from Herring bodies → into the capillary network in the posterior
pituitary.

Neurohypophysis (posterior) – histology

(HB = Herring Bodies, HT = hypothalamo-hypophyseal tract axons, Cap = capillaries)

(Surrounding nucleated cells = pituicytes)

Pars Intermedia – function + histology

● Unknown function BUT cells of the pars intermedia produce melanocyte-stimulating
hormone and endorphins.
● Histology consists of basophils and chromophobes that surround small spaces filled with
eosinophilic colloid.
Lecture 10: Endocrine Glands II

Thyroid gland
● A lobulated endocrine gland surrounded by a thin connective tissue (capsule) located
anterior to the upper trachea (at the front of the neck).
● The follicular epithelium of the thyroid gland secretes 2 hormones (T3, T4) under the
control of TSH secreted by the thyrotrophs of the adenohypophysis.
○ T3 and T3 = regulates metabolism and growth.
● Parafollicular cells (found in and between the follicular epithelium) = secrete
calcitonin in concert with parathyroid hormone → regulates blood calcium
levels.
● The inactive form of T3 and T4 is stored as colloid called thyroglobulin (strongly
eosinophilic).
○ DIFFERENT from the colloid filled cysts of the pars intermedia).

Thyroid gland – histology

● Capsule = outer-most layer consisting of a dense irregular connective tissue.
● Blood vessels = highly-vascularized tissue because the majority of endocrine secretions
directly enter the circulatory system where they act on distant cells.
● Colloid = gell-like substances within the follicles.
● Septa = the connective tissue capsules that invaginate the tissue to form different
lobules.
● Large follicles = functional storage units that contain thyroglobulin (the inactivated forms
of T3 and T4 hormones).

Functional histology of Thyroid gland

● Thyroid follicle = functional units of the thyroid gland.
○ Each follicle is made up of a single layer of cuboidal epithelial cells resting on a
basement membrane = follicular cells.
 ● Follicular cells surround a lumen filled with thyroglobulin (secreted in its storage form).
● In active secretory thyroid glands, follicle cells appear small and taller (indicating active
hormone synthesis).
● In inactive thyroid glands, follicles are large and distended (appears flattened).
● Follicle cells are also present in an extensive capillary network (often seen beneath the
follicular epithelium).
● Parafollicular cells (clear staining cells with prominent nuclei) are also present.

Thyroglobulin production and utilization

1. Thyroglobulin is produced by rER → packaged by
the golgi apparatus → stored in the colloid.
2. Iodide is taken up from the blood → crosses into the
colloid.
3. Thyroglobulin is iodized in the colloid → converts
into T3 and T4.
4. Lysosomes and receptor mediated (5TE) pathways
reabsorb T3 and T4 → releases them into the blood
circulation.

Calcitonin and Parafollicular cells

● Parafollicular cells (C cells) → located in the periphery of the follicular
epithelium + follicle basal lamina.
● No exposure to the follicle lumen.
● Function = secretion of calcitonin (hormone that regulates calcium metabolism).
○ Calcitonin inhibits bone matrix resorption by altering osteoclast function thus
preventing calcium release.
Putting it all together
1. A stimulus (e.g., low body temperature) causes the hypothalamus to secrete
thyrotropin-releasing hormone (TRH) → acts on the anterior pituitary.
2. Thyrotropic cells in the anterior pituitary release thyroid-stimulating hormone (TSH).
3. TSH stimulates follicular cells of the thyroid gland to release thyroid hormone (TH).
4. TH stimulates target cells to increase metabolic activities → resulting in an
increase in basal body temperature.
5. Increased body temperature is detected by the hypothalamus → further
secretion of TRH is inhibited. TH also blocks TRH receptors on the thyrotropic
cells → inhibiting synthesis/release of TSH.
○ Both effects indirectly dampen TH production in the thyroid.

Parathyroid glands
● = Consists of a pair of glands on either
side of the posterior thyroid gland.
● Derived from the third and fourth
pharyngeal pouches (distinct from the
thyroid).
● The parathyroid glands are separated from
the thyroid by the connective tissue
capsule.
○ A thin trabeculae separates the
parathyroid into lobules.
● Functional components of the parathyroid
= closely packed cords of secretory cells
divided into 2 cell types:
○ 1. Principle (chief) cells – secretes
parathyroid hormone
○ 2. Oxyphil cells – unknown function
Parathyroid – histology
● Chief cells and Oxyphil cells are found in large groups of the same cell type separated
by connective tissue septa (containing networks of fenestrated capillaries and lymphatic
vessels).
○ Chief cells = small, polygonal cells with pale staining cytoplasm.
■ Function → secretes parathyroid hormone (PTH).
● PTH regulates calcium and phosphate levels in the blood by stimulating bone resorption
via osteoclasts.
● Chief / Principal cells (CC) contain abundant small secretory granules, large
accumulations of glycogen + lipid droplets.
● Oxyphil cells (OC) have a larger and more eosinophilic staining cytoplasm (more pink)
with no secretory vesicles or rER.

Adrenal glands
● The adrenal (suprarenal) glands are paired organs embedded in the perirenal adipose
tissue at the superior pole of each kidney.
● Has 2 distinct types of endocrine tissue: (1) Cortex and (2) Medulla.
○ Bound together by a dense irregular connective tissue capsule.
● (1) Cortex = secretes steroid hormones of 3 functional classes
○ 1. Mineralocorticoids
○ 2. Glucocorticoids
○ 3. Sex hormones
● (2) Medulla = secretes catecholamine hormones
○ 1. Adrenaline (epinephrine)
○ 2. Noradrenaline (norepinephrine)

Blood supply of the Adrenal Glands

 ● Both glands receive arterial blood from the (1) superior, (2) middle, and (3) inferior
suprarenal arteries.
○ The suprarenal arteries split into many small arteries before entering the
connective tissue capsule:
■ (4) Capsular capillaries (capsular plexus)
■ (5) Cortical capillaries (fenestrated, sinusoidal) – supplies cortex before
draining into the medullary capillaries)
■ (6) Medullary arterioles – supply medullary capillary sinuses
● (7) Venules arising from the medullary capillaries drain into small collecting veins before
joining the central vein.
○ The central vein drains into the left renal vein (left side) and the inferior vena
cava (right side).

Functional zones of the Adrenal Glands

● The adrenal cortex is divided into 3 zones (based on cell arrangements and hormones
they secrete):
○ 1. Zona Glomerulosa = deepest (near the
capsule)
■ 15% of the cortex
■ Arranged in round clusters
■ Secretes mineralocorticoids
(electrocyte and fluid homeostasis)
○ 2. Zona Fasciculata = middle
■ ~80% of the cortex
■ Arranged in parallel cords 1-2 cells
■ Orientated perpendicular to the
capsule
■ Secretes glucocorticoids
(carbohydrates, lipid, and protein
metabolism)
○ 3. Zona Reticularis = most superficial (near
adrenal medulla)
■ ~5% of the cortex
■ Arranged in irregular cords
■ Secrete gonadocorticoids (supplement
gonadal hormone secretion)
● The adrenal medulla lies deep to the cortex; composed of groups of large and
closely packed Chroman cells (neural crest origin) → secretes
catecholamines.

Zona Glomerulosa (adrenal cortex)

● Arranged in irregular ovoid clusters (separated by connective tissue trabeculae that
contain wide capillaries).
● Zona glomerulosa cells are small and pyramidal-shaped with strongly staining nuclei.
 ● Contain abundant sER but little lipid droplets.
● Secretion = mineralocorticoid aldosterone → controls blood pressure by
regulating sodium and potassium levels.
○ Aldosterone secretion is regulated by the renin-angiotensin-aldosterone (RAAS)
system.

Zona Fasciciulata (adrenal cortex)

● Largest of the 3 zones → cells are large and polyhedral shape arranged in
long straight cords (with ne strands of connective tissue containing wide
lumen capillaries).
● Zona fasciculata cells have lightly staining nuclei + pale staining cytoplasm (full of lipid
droplets) + prominent rER and sER.
○ Some cells may be binucleated.
● Secretion = glucocorticoids (primarily cortisol) → regulates the metabolism of
glucose and fatty acids.

Zona Reticularis (adrenal cortex)

● Arranged as anastomosing (cross-connecting) cords of small cells – no longer straight.
 ● Cords are separated by fenestrated capillaries.
● Zona Reticularis cells have densely staining nuclei + less cytoplasm → appear
more closely packed.
○ Contain abundant sER, mitochondria with tubular cristae, little rER.
● Secretion = gonadocorticoids (adrenaladrogens) such as DHEA, but also limited
amounts of glucocorticoids (cortisol).

Adrenal medulla – histology

● Closely packed clusters of chromaffin cells interspersed with sinusoidal capillaries and
extensive collecting veins (draining from the medullary sinuses).
○ Chromaffin cells = larger granular nuclei + extensive basophilic cytoplasm.
○ Numerous myelinated, presynaptic nerve fibers (of sympathetic nervous system)
pass directly into the chromaffin cells.
■ Nerves stimulate the secretion of catecholamines when under acute
physical or psychological stress.
● Distinct smaller chromaffin population cells:
○ Ones with smaller and lighter staining vesicles = secretes adrenaline
(epinephrine)
○ Ones with larger and darker staining vesicles → secretes noradrenaline
(norepinephrine).
Lecture 11: Sensory Systems I (Vision)

Anatomy of the eye

● 2 fluid chambers and 1 vitreous chamber (separated by the lens).
○ Anterior and Posterior uid chambers contain aqueous humour →
nourishes the eye through diusion of nutrients and oxygen, refracts
light, and maintains shape of the eye.
○ Vitreous chamber contains vitreous humour (transparent gel) →
nourishes the eye, refracts light, and maintains shape of the eye.

Eye development
● Optic vesicle → forms the optic cup (neural retina).
● Lens placode → forms the lens pit (lens).

––→

Anatomy of the eye – Sclera

● Made up of 3 layers (each with different structures/functions):
1. Fibrous layer (outer)
2. Vascular layer (mid)
3. Retinal layer (inner)

Fibrous layer
● Provides shape and support.
● Made up of Sclera and Cornea.
○ Sclera (white of eye) = 85% of outer coating, attaches to extraocular muscles (for
eye movement).
○ Cornea (continuous with Sclera) = 15% of outer surface, centrally-located,
transparent, and refracts light.

The Cornea
● Consists of 2 membranes = Bowman’s membrane + Descemet’s membrane.
○ Bowman’s membrane supports the corneal epithelium
○ Descemet’s membrane supports the corneal endothelium
 ● Stromal collagen lamellae are organized orthogonally (right angled) →
contributes to corneal transparency.

Anatomy of the eye – Choroid

● Consists of the Vascular layer (mid).
● The vascular layer is comprised of:
○ Choroid
○ Ciliary Body
○ Iris
● The Choroid = pigmented vascular layer → provides nourishment to outer
layers of retina (retinal pigmented epithelial cells).
● The Iris = denes eye colour by its pigmentation and controls the size of the
pupil → regulate levels of incoming light.

Iris
● A circular structure with a central aperture (the pupil).
● The pupil size is controlled by circular and radial muscle fibers.
○ Circular pupillae muscle = innervated by parasympathetic nervous system.
■ Constricts pupil and limits entering light.
○ Radial pupillae muscles = innervated by sympathetic nervous system
■ Dilates pupil and increases entering light.
Ciliary Body
● Made up of ciliary muscles and ciliary processes.
1. Produces the aqueous humour.
2. Adjusts focal strength of lens by changing its shape (i.e., accommodation).
○ Requires the ciliary muscles and ciliary zonular processes.
● Ciliary muscle = made up of equatorial circular fibers, reticular radial fibers, and
meridional longitudinal fibers.
○ A major component of the ciliary muscle = the sphincter (ring-like) muscle made
up of equatorial circular fibers.

● Suspensory ligaments (zonule bers) = when the ciliary muscle contracts →

zonule tension is relaxed → lens becomes more rounded.
○ Zonules extend from the ciliary body and insert into the lens capsule, holding the
lens in place.

Accommodation
● When objects are distant = zonule bers become tense → attens the lens
shape.
● When objects are near = ciliary body muscle contracts → relaxes the tension
of the zonule bers to the lens → lens shape becomes rounder/thicker/fatter.
○ This changes the focal length of the eye, bringing closer objects into focus.

Anatomy of the eye – Lens

● Lens = a transparent spheroidal structure that transmits and focuses light onto the
retina.
● To work effectively, the lens needs to have the correct size and shape (curvature) +
remain transparent.
● SEM of bovine lens fiber cells:
○ Tightly-packed orientation (honeycomb appearance) → minimized
 intercellular space to reduce light scatter.
○ Hexagonal profile – 2 long and 2 short faces.
■ Membrane protrusions at apex of short faces → interlocking for
correct interdigitation.

● Transverse sections of fibers show their ordered honeycomb packing and interlocking
processes.
● Protrusive processes (ball and socket joints) arise at the angles b/w the long and short
faces and b/w separate short faces along the entire length of the fiber.
○ → Important for cell to cell adhesion (accommodation).
● Lens epithelium = cobblestone-like packing.

Anatomy of the eye – Retina

● Retina layer = light-detecting region of the eye (absorbs entering light).
● Consists of 2 sublayers:
1. Neural layer = contains photoreceptors (light detecting cells).
2. Pigmented layer:
○ Under neural layer attached to choroid
○ Supports neural cells
○ Prevents internal refraction of light
○ Continuous through the whole inner surface of eye (more
anterior eye → progressive loss of neural layer).

Retina
● Optic part of the retina contains:
1. Optic disc/nerve
○ Entry of central retinal artery
○ Blind spot (no light sensing cells)
2. Macula lutea
3. Fovea centralis
○ Presence of high number of light
sensing cells and cones (colour vision)
 ● Layers:
○ Inner limiting membrane
■ Optic nerve fibers
■ Ganglion cell layer
○ Inner plexiform layer
○ Inner nuclear layer
○ Outer plexiform layer
■ Cell bodies of rods + cones
○ Outer limiting membrane
○ Photoreceptor layer
■ Pigmented epithelium
■ Choroid

Visual perception
● Light entering the eye is focused by the cornea and lens to hit the photosensitive rods
and cones of the retina.
● The retinal cells synapse and transmit electro-chemical signals to the lateral geniculate
nucleus (LGN) of the midbrain (via the optic nerve).
○ The optic nerve = made up of ascending axons of the retinal ganglion cells.

Lecture 12: Sensory Systems II (Ocular Lens Pathology)

Ocular lens pathology – Cataract

● Cataract = opacification (“clouding”) of the lens.
○ Loss of lens transparency.
○ Loss of light-focussing ability
● Causes of the loss of lens transparency:
○ Change to lens cells organization
○ Altered lens cell morphology
○ Imbalance of water content (e.g., diabetes)
○ Oxidation of proteins by UV: discolouration
○ Protein unfolding and cross-linking/clumping
○ Reduced protein solubility
● Cataract types are generally classified based on their onset and the location of the
opacification – Senile/Age-related vs. Non-Age related.

Senile/Age-related Cataract
● = 99% of all cataract cases.
● Causes: increasing age, family history, systemic diseases (diabetes), medications,
radiation, trauma, eye surgery.
 ● 3 primary types (based on their location):
1. Nuclear sclerotic cataract
2. Cortical spoking cataract
3. Subcapsular cataract – Anterior and Posterior forms
● Nuclear sclerotic cataract:
○ “Sclerotic” = becoming rigid.
○ Most common type of age-related cataract.
○ Impacts the center of the lens/nucleus.
○ Hardening and discolouration of nucleus (brown nucleus)
○ → Blurred vision and loss of colour perception.
● Cortical spoking cataract:
○ Start as white streaks/spokes on rim of lens.
○ Swelling of cortex.
○ Separation of fibers due to change in water.
○ → Causes light scatter, glare, and ‘halo’ eect.
● Posterior subcapsular cataract:
○ Back of lens becomes cloudy.
○ Granular deposits.
○ Leads to blurred vision.
○ Seen in diabetics and steroid users.

Non-Age-related Cataract
● Due to a genetic disorder, injury, or medication use.
● Congenital cataract:
○ Lens/eye development takes place after 3-4 weeks gestation.
○ Present at birth or early childhood (secondary) due to chromosomal mutation
(inherited) or systemic infection/virus.
● Radiation cataract: exposure to radiation → damage to lens proteins.
● Secondary cataract: may develop due to eye injury, eye surgery, or other relatable
diseases.

Loss of lens transparency

● Lens is ⅔ water and ⅓ protein.
● Due to changes to lens proteins.
● Lens proteins:
○ 90% are soluble (ɑ–, β–, �–crystallins).
■ Contributes to transparency of lens.
○ 10% are water insoluble.
■ Urea soluble (cytoskeletal, e.g., actin)
■ Urea insoluble (membrane proteins, e.g., MIP)
○ With age, there is an increase in insoluble proteins.
■ Leads to precipitation of proteins = cortical cataract.
● Also due to change in lens cell organization and altered lens cell morphology.
Cataract surgery treatments for all types
1. Curvilinear capsulorhexis (laser-assisted)
2. Phacoemulsification
3. Insertion of intraocular lens

Epithelial-Mesenchymal Transition (EMT)

● Stationary epithelial cells transform into migratory mesenchymal cells (e.g., embryonic
development).
● These migratory cells can invade tissues and form organs in new places.
● Critical process during development = formations of mesoderm and neural crest cells.
○ EMT during gastrulation – formation of mesoderm by mesenchymal cells
delaminating from the epiblast.
○ EMT during neurulation – formation of neural crest cells from the dorsal region of
the neural tube.
● In adults, EMT can be seen in:
○ Wound healing
○ Cancer metastasis (to form secondary tumours)
○ Fibrotic pathologies (e.g., cataract)

Summary
● EMT leads to altered lens structure.
● Altered lens structure leads to lens dysfunction.
● Dysfunctional lens = pathology (i.e., cataract).
● Cataract surgery can lead to EMT and secondary cataracts (posterior capsular
opacification (PCO)).

Lecture 13: Male Reproduction I

Male reproductive system

● Includes:
○ Testes
○ Spermatic ducts
■ Epididymis
■ Ductus deferens (vas deferens)
■ Ejaculatory ducts
○ Accessory sex glands
■ Seminal vesicles
■ Prostate
■ Bulbourethral glands
○ External genitalia
■ Penis
■ Scrotum
 ● Functions:
○ Spermatogenesis
○ Production of seminal fluid
○ Steroidogenesis
○ Sex
○ + Passage of urine via urethra

Testes
● Site of spermatogenesis and steroidogenesis.
● Extra-abdominal location (in humans).
○ Descend from abdominal cavity during embryonic development due to action of
testosterone.
○ Brings ducts, muscles, blood vessels, lymphatics, nerves and extension of
peritoneum (tunica vaginalis).
● Maintains temperature 2-3°C below body temperature.
○ Required for spermatogenesis, not necessary for steroidogenesis.
○ Contraction of cremaster muscle (in response to ambient temperature)
controls position → controls temperature.

Testes – tunics
● Multilayered tunica covers the testes.
○ Tunica vaginalis:
■ Parietal and Visceral layer.
■ Remnant of peritoneum.
■ Serous membranes lining testes and interior of scrotum.
■ Produce serous uid → reduce friction and facilitate movement.
○ Tunica albuginea:
■ Unusually thick (dense connective tissue capsule).
■ Protective (forms connective tissue septa).
○ Tunica vasculosa:
■ Inner layer contains blood vessels
● Lobules of testes:
○ Seminiferous tubules:
■ Highly convoluted
■ ~50cm long, 150-250μm
diameter
■ Site of spermatogenesis
○ Connective tissue stroma
■ Leydig cells
■ Site of steroidogenesis
Leydig cells
● Large polygonal cells that are eosinophilic.
● Has lipid droplets and lots of sER.
○ Enzymes in sER synthesize testosterone from cholesterol.
● Secretion of testosterone begins in early fetus (via gonadal development).

Testosterone
● Secretion begins from early fetus.
○ Required for sexual dimorphism → stimulates gonadal development
and descent of testes.
● Inactive from 5 months (fetal life) → puberty.
● Secretions increase during puberty:
○ Enlargement of penis, testes, and prostate.
○ Initiation of sperm production.
○ Initiation of accessory sex gland secretions.
○ Development of secondary sex characteristics
● Secretion continues throughout adulthood:
○ Essential for maintenance of above.
○ Maintenance of bone and muscle strength.
○ Erectile function.

Seminiferous tubules and Spermatogenesis

● Spermatogenic epithelium = complex stratified epithelium that contains Sertoli cells and
Spermatogenic cells.
● Myoid cells:
○ Contractile cells surrounding each seminiferous tubule.
○ Under basal lamina of spermatogenic epithelium.
○ Peristaltic contractions → moves sperm and testicular uid through
tubules to excurrent ducts.

Spermatogenic epithelium
● Sertoli cells = true epithelium that act as supporting cells.
● Spermatogenic cells = germ cells.
○ Stem cells (spermatogonia) undergoing spermatogenesis to turn into mature
sperm.
○ Migrate towards lumen as they mature.
● Spermatogenesis
○ Process consists of Mitosis, Meiosis, and Spermiogenesis.
■ Spermiogenesis = nal dierentiation → involves morphological
transformation from round cell into mature sperm.
Spermatogenesis

Spermatogonia
● Large cells with large round nuclei that sit on the basal lamina of seminiferous tubules.
● 3 types:
1. Type A (Dark/Light):
a. Dark (stem cell reserve)
i. Mitosis to replace themselves and maintain stem reserve.
b. Light (renewing stem cells)
i. Committed to differentiate, but first undergo multiple mitotic
divisions to increase number.
2. Type B = last step in spermatogonial phase. Has condensed chromatin.

Spermatocytes
● Primary spermatocytes = produced by type B spermatogonia undergoing mitosis.
○ Largest cells with large round nuclei and clumped chromatin.
○ Immediately replicate their DNA and enter prophase I of meiosis (22 days in).
○ Crossing over occurs → creating new combinations of DNA with
chromosomes.
● After first meiotic division = secondary spermatocytes.
○ Immediately enter prophase II of meiosis (without any DNA replication).
○ Rapidly completes 2nd meiotic division → forms spermatids.

Spermatids
● No changes to DNA. No cell division.
● Undergoes Spermiogenesis = ‘morphological transformation’ (differentiation) into mature
sperm.
 ○ Extensive cellular remodeling.
○ Spermatids physically attaches to Sertoli cells during the transformation.
○ Start as small round cells with round nuclei → nucleus condenses →
forms acrosome → develops agellum → cytoplasm reduces → removes
excess organelles (ribosomes, ER, golgi, etc.).

Spermatozoa
● Final maturation occurs in the epididymis.
● Streamlined morphology → must swim through uid in the female
reproductive tract to reach the oocyte.
● Structure:
1. Head
○ Acrosome = contains enzymes to penetrate the zona pellucida of oocyte
for fertilization.
○ Nucleus = extremely condensed and inactive haploid.
2. Tail
○ Neck = contains centriole.
○ Midpiece = contains mitochondria (ATP / energy synthesis for movement).
○ Principal / End piece = flagellum containing axoneme.
● Human sperm have terrible morphology → anything over 4% normal is
classied as “normal sperm morphology range”.

Meiosis in Spermatogenesis
● = one of the mechanisms that ensures genetic diversity in sexual reproduction (for
evolution).
● Meiosis → determination of ospring’s sex.
○ Divides X and Y chromosomes into sperm → sex determination.
● But through meiosis, spermatogenic cells become genetically different to itself =
antigenic.
Sperm determine sex of offspring
● Spermatogonia are diploid = 23 pairs of chromosomes (46 chromatids total).
○ Chromosome #23 (“sex chromosome”) = X + Y
○ 1 chromatid of maternal + paternal origin.
● Duplication of genetic material = 23 pairs → 46 chromosomes total (92
chromatids).
○ Crossing over: exchange of DNA b/w chromosomes pairs.
○ Division: maternal/paternal chromosomes randomly allocated to daughter cells
(including X and Y).
● After Meiosis I → cells become haploid (23 individual chromosomes; 46
chromatids).
● During Meiosis II → the 46 sister chromatids separate.
● After Meiosis II → cells remain haploid (23 chromosomes; 23 chromatids).
○ Each spermatid contains 23 chromatids with mixed DNA.
○ Differentiate into sperm (via spermiogenesis).
○ Fertilize a (haploid) egg → creating 23 new pairs of chromosomes.

Sertoli cells
● Supporting cells
○ Processes of sertoli cells surround spermatogenic cells for duration of
spermatogenesis.
○ Spermatids attached to the plasma membrane of the sertoli cell (via specialized
junctions during final maturation).
● Rests on basal lamina.
● Apical surface faces lumen of seminiferous tubules.
● Large, pale, ovoid or triangular nucleus with prominent nucleolus.
● Extensive sER.

● Function:
○ Provide nutrients and growth factors.
○ Remove wastes – phagocytose components of spermatids in final stage of
 spermiogenesis.
● Hormone sensitive (stimulated by FSH and testosterone).
● Secretory cells:
○ Exocrine cells = secretes uid → seminiferous tubules, and facilitates
movement of sperm along tubules → ducts.
○ Endocrine cells = secrete several hormones including inhibin (negative feedback
for FSH).
● Blood-testis barrier.

Blood-testis barrier
● Unique sertoli to sertoli cell junctional complex.
○ Basolateral
○ Tight junctions (zonula occludens)
● Segregates luminal uid → allows strict control over its composition.
● Prevents passage of toxic agents from blood into tubules.
● Segregates pre-meiotic and post-meiotic entities.
○ Spermatogonia on the outside (extracellular), and the rest on the inside
(intracellular).
○ Post-meiotic = different DNA (antigenic).
■ Isolates post-meiotic from the immune system → ensures
protection from immune response for these foreign cells.
■ Antigens produced by sperm cannot enter circulation.
■ Circulating antibodies cannot reach sperm.
■ If blood-testis barrier fails → anti-sperm antibodies are produced
(can cause infertility).
● Early primary spermatocytes pass through junctional complex.

Summary
● Spermatogenesis takes 74 days in humans.
○ From spermatogonium mitosis → spermatid release from sertoli cell
surface.
○ Further 12 days to pass through epididymis and mature.
● Spermatogenesis starts at puberty and continues throughout adulthood.
○ ~300 million sperm produced per day.
○ 40-300 million/ml of ejaculate = normal
○ <10 million/ml = low sperm count.
● But only ~200 reach the oocyte and only one can enter + fertilize.

Lecture 14: Male Reproduction II

Pathway of sperm
● Synthesized in Testes.
 ● Stored and matured in the Epididymis.
● Ejaculation forces sperm into Vas Deferens.
● Meets with seminal vesicles to form Ejaculatory Duct.
● Passes through the prostate and empties into the Urethra.
● Seminal plasma is added to the ejaculate via ducts and accessory sex glands:
○ Seminal vesicles (~70%)
○ Prostate (~30%)
○ Bulbourethral gland (<1%)

Ejaculation
● 2 phases:
1. Emission:
○ Contractions in vas deferens (sperm), seminal vesicles, and
prostate → expel uid.
■ Combined and stored in prostatic urethra (semen).
○ Contractions in bulbourethral gland.
2. Expulsion:
○ Often associated with orgasm.
○ Contractions in smooth muscle of urethra + rhythmic
contractions in striated muscles of perineum → propel semen
from prostatic urethra.
○ Ejection of combined semen through penile urethra.

Epididymis
● Highly coiled tube (~6m long) with multiple profiles.
○ Lined with Pseudostratified Epithelium with
basal cells and principal cells (covered in
stereocilia for absorptive function).
■ Absorbs remaining fluid coming from
seminiferous tubules.
■ Phagocytosis (breakdown) of material
released by maturing sperm and any
degenerates.
■ Secretion of factors that aid in sperm
maturation.
○ Surrounding smooth muscle
■ Head and Body → peristalsis to move sperm along.
■ Tail → intense contractions at ejaculation
● Divided into Head, Body, and Tail.
○ Immature sperm (incapable of fertilization) enter at head.
○ Sperm takes ~12 days to travel through and undergo further maturation.
■ Gain motility.
■ Further condensation of nucleus.
■ Further reduction of cytoplasm.
 ■
Decapacitation = modification of acrosome (sperm head) to inhibit
fertilizing ability.
● This is reversed during Capacitation in the female reproductive
tract.
● Mature sperm → expelled from tail into vas deferns at ejaculation.

Vas Deferens (Ductus Deferens)

● Muscular tube (~30cm long)
● Strong peristaltic contractions at ejaculation (emission) carry sperm from
epididymis → seminal vesicles.
○ Travels through spermatic cord alongside testicular artery/veins.
● Histology:
○ Lined by pseudostratified epithelium covered stereocilia (similar to epididymis).
○ Folded lumen (due to contraction of muscle during tissue fixation).
○ Very muscular wall – 3 layers of smooth muscle:
■ Inner longitudinal
■ Middle circular
■ Outer longitudinal
○ Testicular artery and veins.

Vasectomy
● Vas deferens cut for male sterilization.
● Relatively safe and reliable contraception.
● Possible to reverse (but unreliable).
○ Reversible male contraceptives largely target vas deferens.
● Sperm leak through cut ends, exposes spermatozoal antigens to immune
system → anti-sperm antibodies produced.

Seminal vesicles
 ● Paired highly folded tubular glands.
● Short excretory duct combines with vas deferens to form ejaculatory duct.
● Produces 70% of seminal plasma (under testosterone control).
○ Fructose (large amount).
○ Amino acids, proteins, enzymes, vitamin C, and prostaglandins.
● Functions:
○ Fructose = main energy source for sperm.
○ Alkaline uid → neutralizes acidic vaginal pH to facilitate sperm
survival.
○ Suppresses immune function in female reproductive tract.
● Histology:
○ Highly folded tubular glands – one continuous lumen (but look like multiple due to
the folds).
○ Pseudostratied OR simple columnar epithelium → highly secretory and
contain many secretory granules, abundant golgi, and rER.
○ Lamina propria = very elastic connective tissue.
○ Thick smooth muscle wall → contraction during ejaculation (emission
phase).

Prostate
● Glandular organ that surrounds the neck of the bladder and urethra.
○ 30-50 compound tubuloalveolar glands.
○ Produces ~30% of seminal plasma (under testosterone control) = prostatic acid
phosphatase, fibrinolysin, citric acid, and prostate-specific antigen.
● Functions:
○ Enzymes liquify semen after ejaculation.
○ Alkaline neutralizes acidic vaginal pH.
● Prostatic urethra allows passage of urine and semen.
○ Contraction of bladder neck at ejaculation prevents urine release and retrograde
ejaculation.
● Histology:
○ Surrounded by bromuscular stroma → contractions at ejaculation
(emission) pump alveolar secretions into urethra.
○ Transitional epithelium lines the prostatic urethra (runs through middle).
 ■ Glands of prostate empty into prostatic urethra.
■ Ejaculatory ducts (from seminal vesicles) also empty into prostatic
urethra.

● Tubuloalveolar glands (histology):

○ Generally lined by simple columnar epithelium (but can vary – simple cuboidal to
pseudostratified).
○ Very irregularly-shaped lumen (with connective tissue papillae).
○ Alveoli can contain prostatic concretions (i.e., ‘corpora amylacea’).
■ = concentric lamellated material.
■ Precipitated prostatic secretions (stored in the lumen)
■ Can become calcified.
■ Appear during fetal development (common in older ages).
■ No known functional consequence (may appear in semen).
○ Fibromuscular stroma (connective tissue + smooth muscle cells).
Bulbourethral glands
● Compound tubuloalveolar glands
● Histologically similar to other mucus-secretory glands → acini of columnar,
mucus-secreting cells.
● Divided into lobules and surrounded/separated by smooth muscle.
● Contraction during ejaculation (emission stage) pushes mucus secretion →
urethra.

Penis
● Passage of urine and semen.
● Contains vascular erectile tissues (NO bone):
○ Engorgement with blood causes erection.
○ For human reproduction, erection allows vaginal penetration during intercourse
and ejaculation of semen into the vagina (+ on the cervix). Sperm is transported
through the female reproductive tract (largely by their own activity) to the site of
fertilization in the fallopian tube.
Urethra
● Epithelium changes from bladder → end of penis.
○ Neck of bladder = transitional.
○ Prostatic urethra = transitional.
○ Membranous + most of penile urethra = pseudostratified.
○ Terminal portion of penile urethral = non-keratinized stratified squamous.
● Epithelium of all spermatic ducts = pseudostratified.

Penile cylindrical vascular erectile tissue

● Consists principally of 3 cylindrical masses of vascular erectile tissue:
○ 2 dorsal = corpora cavernosa → primarily responsible for erection (90%
of blood).
○ 1 ventral = corpus spongiosum → contains urethral.
● Surrounded by dense fibroelastic layer:
○ Tunica albuginea
○ Binds the 3 cylindrical mass together by forming a capsule around each.
● Covered by loose connective tissue and thin skin.

Corpus cavernosum
● Surrounded by thick dense connective tissue (tunica albuginea)
● Many wide irregularly-shaped vascular spaces.
○ Cavernous sinuses – 90% of blood.
○ Lined with endothelium.
● Connective tissue trabeculae between = contains smooth muscle, helicine arteries,
nerves.
● Veins sit at edge of tunica.
Corpus spongiosum
● Surrounding tunica albuginea is thinner and more elastic.
○ Prevents compression of urethra during erection → allows semen to be
released at ejaculation.
● Contains similar cavernous sinuses and connective tissue septa.
○ Only 10% of blood during erection.
● Contains penile urethra.
● Some small mucus glands in corpus spongiosum empty into the urethra.

Erection
● Parasympathetic stimulating initiates erection.
○ Dilation of helicine arteries.
○ Increased blood flow.
○ Relaxation of smooth muscle cells in trabeculae (enhanced by Viagra).
○ Cavernous sinuses fill with blood.
○ Corpora cavernosa expand.
○ Veins compress against tunica albuginea → blocking venous outow.
○ = Erection achieved (via hydraulic pressure).
● Sympathetic stimulation ends erection.
○ Constriction of helicine arteries.
 ○ Contraction of smooth muscles in trabeculae.
○ Decreased blood flow to cavernous sinuses.
○ Decreased pressure on veins → unblocking venous unfollow.
○ Blood drains.
○ → Erection subsides (penis returns to accid state).
■ In flaccid penis, smooth muscle cells under tonic contraction limits blood
flow into sinuses.

Penis – other features

● Penis contains extensive nerve fibers.
● Many Pacinian corpuscles (= nerve endings
responsible for sensitivity to touch and
pressure).
● 2 striated muscles at the base of penis:
○ Bulbospongiosus
○ Ischiocavernosus
● Rhythmic contractions increase
pressure in corpus spongiosum →
propels semen through urethra
(expulsion phase of ejaculation).

Lecture 15: Sensory Systems III (Touch, Pain, Taste, & Smell)

Touch and pain

● Skin (all layers) contains several types of sensory structures and specialized receptors:
○ Merkel disc
○ Meissner corpuscle
○ Pacinian corpuscle
○ Free nerve endings
○ Ruffini corpuscle
● Signals from the skin are conveyed by:
○ Mechanoreceptors → respond to physical changes (including touch,
pressure, vibration, and stretch).
■ Pacinian corpuscles – detect vibration, course touch, and pressure
● Located deep in the dermis.
■ Meissner corpuscles – detect indentation and slipping of objects.
● Located in dermal papillae.
■ Merkel complexes (cells to discs) – detect fine touch, structure, and
texture.
● Located in the basal epidermis.
■ Ruffini corpuscles – detect stretch.
● Located in the middle of the dermis.
○ Thermoreceptors → respond to temperature uctuation.
 ■ Body has both warm and cold thermoreceptors → these
receptors display a constant discharge to their specic
temperatures. When the opposite temperature is experienced,
there is a sudden ceasing of receptor discharge.
■ Found throughout the skin (on nerve endings):
● Heat receptors = located close to skin surface.
● Cold receptors = located deeper in the dermis.
○ Nociceptors → responds to pain perception (related to temperature,
pressure, and chemicals).
■ Receptors only signal when the body has reached a point of ‘extreme’
tissue damage.
■ Located throughout the dermis with regional variations.

Taste
● Taste buds = ovoid structures within the stratified epithelium.
○ ~250 taste buds are present on the lateral surface of each vallate (circumvallate)
papilla.
○ Many others present on fungiform and foliate (but not keratinized filiform)
papillae.
○ A taste bud has 50-100 cells – half are elongated taste (gustatory) cells (7-10 day
lifespan).
● The base of each bud rests on the basal lamina and is entered by aerent
sensory axons → forms synapses with the taste cells.
● At the apical ends of the taste cells = microvilli project toward the ‘taste pore’ (2µm wide
opening).
○ Molecules or tastants (dissolved in saliva) contact the microvilli through the pore
and interact with cell surface taste receptors.
● Taste buds detect at least 5 categories of tastants:
○ Sodium ions (salty)
○ Hydrogen ions from acid (sour)
○ Sugars + related compounds (sweet)
○ Alkaloids + certain toxins (bitter)
○ Amino acids; such as glutamate and aspartate (savory)
● Detection:
○ Salt and sour tastes are produced by ion channels.
○ The other taste categories are mediated by G-protein coupled receptors.
● Perception = receptor binding produces depolarization of the gustatory cells
→ stimulates the sensory nerve bers that send information to the brain for
processing.
○ Conscious perception of tastes in food requires olfactory and other sensations (in
addition to taste bud activity).
Smell
● Olfactory bulb = olfactory cells (slender bipolar neurons that span the width
of the epithelium) are receptor cells that bind odoriferous substances →
converts them to nerve impulses.
● Odorant molecules (OMs) interact with olfactory receptors (ORs) located on the cilia of
olfactory sensory neurons (OSN).
○ The plasma membranes of cilia contain a family of transmembrane proteins that
constitute odor (chemosensory) receptors.
● Binding of an odorant to a specic olfactory receptor → induces signaling of G
proteins → cyclic AMP-mediated opening of cyclic nucleotide-gated ion
channels (accompanied by Ca2+ and Na+) → depolarizes the olfactory
receptor neuron → initiates an action potential that is transmitted to the brain
→ odorant molecules are then encoded by the unique pattern of activity they
generate in the brain.
Lecture 16: Sensory Systems IV (Hearing & Equilibrium)

Hearing
● Anatomy of the ear:
○ Outer ear – consisting of the auricle and external auditory meatus.
■ Responsible for transferring sound waves from the environment to the
middle ear.
○ Middle ear – consisting of the tympanic membrane and auditory ossicles.
■ Responsible for amplifying sound waves into strong signals for the
hearing receptors to detect.
■ Also contains the eustachian tube (auditory tube) that connects
with the pharynx → equalizes air pressure in the skull.
○ Inner ear – consisting of the cochlea, 3 semicircular canals, and
vestibulocochlear nerves.
■ Responsible for using mechanoreceptors to detect stimuli for hearing (in
cochlea) and equilibrium (in semicircular canals) + sending the nerve
impulses through the vestibulocochlear nerve to the brain.
● Auditory ossicles (tiny ear bones in middle ear) = includes the malleus, incus, and
strapes.
○ All articulated to one another but not to the skeleton.
○ The malleus is attached to the tympanic membrane.
○ The strapes is attached to the cochlea.
● When the ossicles vibrate → waves in the endolymph uid inside the cochlea
are generated.
● Endolymph waves bend the stereocilia of the hearing receptors (hair cells) located in the
 organ of corti on the basilar membrane.
○ Bending of hair cells → generates nerve impulses which reach the
cerebrum via the cochlear nerve (via mechanoreceptors).

Role of the Cochlear Duct in hearing

● High-frequency sound waves → generate pressure waves that displace the
basilar membrane near the base of the cochlea (near the oval window).
● Medium-frequency sound waves → generate pressure waves that displace the
membrane at dierent points along the central region of the cochlea.
● Low-frequency sound waves → generate waves that displace the membrane
near the helicotrema (at the apical end of the cochlea).

Balance
● Utricle and Saccule = small sac/pouch that monitors static position and linear
acceleration of the head.
○ Maculae in the walls of the utricle/saccule → small areas of columnar
neuroepithelial cells innervated by branches of the vestibular nerve.
■ Lies in the perpendicular plane.
○ Hair cells (on the macula) act as ‘mechanoelectrical transducers’ =
converts mechanical energy → electrical energy (nerve action
potentials).
■ Each has an apical hair bundle = a rigid cilium (‘kinocilium’) and a bundle
of rigid unbranched stereocilia.
● The tips of these are embedded in a thick gelatinous layer of
proteoglycans (called otolithic membrane).
○ The interconnecting membrane of utricle/saccule = very thin connective tissue
sheath lined with simple squamous epithelium bound to the periosteum of the
bony labyrinth (by strands of connective tissue containing microvasculature).

Balance – Hair cells

● 2 types of hair cells in the maculae and cristae ampullares:
○ Type I hair cells = rounded and enclosed within a nerve calyx on the afferent
fiber.
○ Type II hair cells = columnar and associated with typical bouton synaptic
connections to their afferents.
○ (Both types are also associated with efferent fibers).
● Head movements → cause the stereocilia bundle to be deected toward the
kinocilium → produces tension in the tip links → transduces to electrical
activity (by opening of adjacent cation channels).
○ Entry of K+ depolarizes the cell → opening voltage-gated basolateral
Ca+ channels → stimulates the release of neurotransmitters.
○ When this movement stops = the cells quickly repolarize.
● Head movements in the opposite direction (away from the kinocilium) →
produces slackness on the tip links → closes the mechanically gated apical K+
 channels completely → produces hyperpolarization → inhibits transmitter
release.
○ Different numbers of afferent and efferent fibers on the hair cells that respond
differently to endolymph movements (due to their positions within the maculae
and cristae).
○ Sensory information (produced collectively by these cells) can be
processed by the vestibular regions of the brain → used to help
maintain equilibrium.
● Stereocilia occur in rows of increasing height (with the tallest next to the single kinocilium
on one side of the cell).
○ The end of each stereocilium has a dense region containing cation
channels and proteins involved in mechanoelectrical transduction
(converts the mechanical energy → electrical activity).
○ Neighbouring stereocilia are connected by proteins of various side links.
○ Changes in the tension of the tip links (caused by bending of the hair bundle) =
opens or closes the adjacent mechanically gated K+ channels and change the
afferent synaptic activity of the hair cell.

Semicircular ducts (rotational head movements)

● Ducts extend from and return to the wall of the Utricle.
● Each of the semicircular ducts has an expanded end (called the ‘Ampulla).
● Ducts lie in 3 different spatial planes (at approximately right angles) to one another.
● Each semicircular duct has one enlarged ampulla end containing hair cells + supporting
cells on a crest of the wall (called the ‘Crista Ampullaris’).
○ Each crista ampullaris = perpendicular to the long axis of the duct.
● Histologically similar to maculae (but the proteoglycan layer is thicker and lacks otoliths).
● The cupula extends completely across the ampulla; contracting the opposite nonsensory
wall.
○ The cupula is moved by endolymph movement within the semicircular duct.

Lecture 17: Female Reproductive System I (Ovaries)

Ovarian Hormones
● Estrogens
○ Promotes growth and maturation of sex organs.
○ Expression of sex characteristics at puberty.
○ Breast development and adipose (fat) accumulation.
● Progesterone
○ Prepares uterus for pregnancy.
○ Prepares mammary gland for lactation.
● Gonadotropes (basophils) → FSH, LH
● Lactotropes (acidophils) → prolactin
Ovary
● Gametogenesis specifically oogenesis
● Steroidogenesis
● Medulla & cortex

Structure of Ovary
● Germinal epithelium
● Tunica albuginea
● Cortex → follicles
● Medulla → large blood vessels

Germ cell migration

● Migrates from embryonic yolk sac → into embryonic gonald

Oocyte numbers
● 600,000 - 800,000 primary oocytes are present at birth.
○ Arrested at prophase I
● About 400 ovulated over a lifetime.

Primordial Follicles
● From 3rd month of fetal development.
 ● Independent of gonadotrophin stimulation.
● Oocyte → simple squamous layer follicular cells.

Primary Follicle
● Cuboidal follicular / granulosa cells (1 to several layers).
● Formation of zona pellucida.
● Stromal cells surrounding follicles become theca interna and theca externa cells.
● Moves deeper into ovary (due to proliferation of granulosa cells).

Early Primary Follicle

● Basal lamina b/w follicular cells and stroma.
● Formation of zona pellucida:
○ Secreted by oocyte.
○ Zona pellucida-1, -2, -3, -4.
○ Homogenous acidophilic.
○ Refractile border.

Late Primary Follicle

● Several layers of granulosa cells.
● Has gap junctions b/w granulosa cells and oocyte.
Theca Folliculi
● Theca interna:
○ Highly vascularized
○ Cuboidal secretory
○ Steroid-producing
○ LH receptors → synthesizes and secretes
androgen.
● Theca externa:
○ Outer layer of connective tissue
○ Collagen and smooth muscle fibers

Secondary Follicle
● Granulosa cells 6-12 layers deep.
● Fluid-filled cavities among granulosa cells:
○ Liquor folliculi
○ Hyaluronan-rich fluid
● Oocyte = 125µm diameter (no further growth).
● FSH required for development.

Estrogen production
● Theca interna cells:
○ LH receptors
rub ○ Androgens
● Granulosa cells: 2 gohere
○ FSH receptors

IIS ○ Converts testosterone into estrogen.

Mature Graafian Follicle

go intobtwnimply
● Large (10mm+ diameter).
● Single fluid-filled antrum takes up most of the follicle volume.
● Specializations of granulosa cells:
○ Cumulus oophorus
○ Corona radiata

to
 i D

Ovulation
● High level of estrogens (from follicles) → surge in LH and FSH.
○ Proteolytic enzymes.
○ Resumption of meiosis 24 hours before ovulation.
IIjated ○ Secondary oocyte → arrested at metaphase II until fertilization.
● Oocyte + cumulus oophorus + corona radiata + ovulated fluid

Follicular Fluid Components

● Lots of components =

● Use of follicular fluid analysis is an indicator of pregnancy outcome.

Corpus Luteum
● Endocrine organ.
● Remaining granulosa and theca cells undergo ‘luteinisation’.
● Cells increase in size by accumulating lipid.
It means
○ Steroid secreting → abundant sER and mitochondria with tubular
cristae.
● Lipochrome = lipid soluble pigment with yellow appearance.
● Granulosa lutein cells:
○ Develops from granulosa cells of follicle.
○ 30µm diameter.
○ Secrete estrogens, progesterone, and inhibin
● Theca lutein cells:
○ Develops from theca interna.
○ Smaller 15 diameter (darker staining)
○ Secretes androgens + progesterone.

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Corpus Albicans
● If NO fertilization = corpus luteum degenerates by about day 10.
○ Degenerating cells leads to intracellular hyaline material accumulation.
● White scar in ovary.
Atretic Follicles
● Occurs at any stage.
● Majority of follicles undergo atresia.
● Apoptosis of granulosa cells.
● Degeneration and autolysis of oocyte.
● Zona pellucida folded → collapses → phagocytosed by macrophage.
● Basement membrane forms glassy membrane (wavy hyaline structure).

The Ovary – Ovulation of Oocyte and Hormone Secretion

● In follicular phase:
○ FSH and LH (pituitary hormones in the blood) stimulate follicle development
○ Growing follicles secrete estrogen
● In luteal phase:
○ LH surge triggers ovulation
○ Corpus luteum secretes estrogen and progesterone
● → Estrogen and Progesterone promote growth of the endometrium.

Lecture 18: Female Reproductive System II (Uterine tube, Mammary gland)

Uterine Tubes
● Transports ovulated ovum.
● Consists of Infundibulum, Ampulla, Isthmus, and Intramural.

Wall of Uterine Tube

● External serosal layer → mesothelium + thin layer of connective tissue.
● Muscular layer → inner circular + outer longitudinal.
 ● Uterine tube mucosa:
○ Highly-folded and highly vascularized.
○ Simple columnar epithelium → has ciliated cells and non-ciliated peg
cells.

Ampulla of Uterine Tube

● More numerous and complex folding of mucosa than isthmus.
● Longest region (⅔ of length).
● Site of fertilization.
Hormonal Regulation of Uterine Tube
● Hypertrophy during follicular phase.
● Atrophy during luteal phase.
● Estrogen → ciliogenesis.
● Progesterone → increase in secretory cells.
● Peak height of epithelial cells = 30µm (at time of ovulation).
○ Half height just before menstruation.

IVF Medication effects on Ampulla of Uterine Tube

● Changes in ampulla of uterine tube after multiple rounds of Controlled Ovarian
Hyperstimulation (COH):
○ Used in IVF to increase oocyte production.
○ Mainly affects cilia and mitochondria within cells.

Mammary Gland Development

● During embryological development:
○ Mammary ridges
○ Normally only 1 develop on each side
● Until puberty:
○ Similar development
 ● At puberty:
○ Males → testosterone inhibits further growth
○ Females → estrogen stimulates further development
■ Ducts extend and branch
■ Proliferation of epithelial cells
● In Adulthood: complete ductal architecture is established.

Adult nipple
● Opening of lactiferous ducts.
● Sebaceous glands, sweat glands, and Montgomery glands (intermediate b/w sweat
glands and mammary glands).
● Nerves.

Mammary Gland – Adult (Inactive)

● Tubuloalveolar glands.
● Derived from modified sweat glands.
● 15-20 irregular lobules.
● Radiate from mammary papillae (nipple).
● Duct → sinus → terminal duct lobular unit (TDLU).
○ Lactiferous duct = keratinized stratified squamous epithelium.
○ Lactiferous sinus = 2 layers of cuboidal epithelium.
○ Duct = simple columnar or cuboidal epithelium.
○ Terminal duct lobular unit (TDLU):
■ Successive branching of lactiferous ducts.
■ Terminal ductules (or secretory alveoli).
■ Intralobular collecting duct.
■ Intralobular stroma.
● Cell types:
1. Glandular epithelial cells → lines duct.
2. Myoepithelial cells → between epithelial cells and basal lamina.
Contraction leads to milk ejection.
Inactive Mammary Gland

Mammary Gland –
Menstrual Cycle
Changes
1. Follicular
phase:
○ Intralobular stroma = less dense.
○ Terminal ductules = cuboidal cells with NO lumen.
2. Luteal phase:
○ Epithelial cells increase in height.
○ Lumina appears in ducts → some secretion.
○ Oedematous connective tissue → may explain breast tenderness and
increase size during luteal phase.

Hormonal influences on mammary development

● Complete morphological and functional is achieved by:
○ Estrogen and progesterone (from corpus luteum and placenta).
○ Prolactin (from pituitary gland).
○ Gonadocorticoids (from adrenal cortex).
Mammary Development during Pregnancy
1. First trimester:
○ Elongation and branching of terminal ductules.
○ Proliferation and differentiation of epithelial and myoepithelial cells (in terminal
ductules).
2. Second trimester:
○ Alveoli form from terminal ductules.
○ Immune cell infiltration.
○ Growth of alveoli → increases mass of breast.
3. Third trimester:
○ Maturation of alveoli.
○ Glandular epithelial cells develop
■ Cuboidal with basal nuclei.
■ Secretory vesicles and lipid droplets.
○ Breast size increase due to:
■ Hypertrophy of secretory cells.
■ Accumulation of secretory cells.

Late pregnancy

At Birth
● Prolactin
and human
placental
lactogen →
suppressed
during pregnancy by estrogen and progesterone.
● Placenta is delivered → drop in estrogen and progesterone.
● Prolactin → milk production.
● Oxytocin → myoepithelial cell contraction.

Production of Milk
● Merocrine secretion:
○ Protein component
○ Extensive rER
 ○ Secretory vesicles to golgi
○ Packaged for exocytosis
● Apocrine secretion:
○ Fatty or lipid component of milk.
○ Lipid droplets are pinched off the surface.

Lactating Mammary Gland

Initiation of Lactation
● Suckling → activation of nipple
mechanoreceptors → signals to the
hypothalamus → inhibits prolactin-inhibitory
factor (dopamine).
○ Release of prolactin from anterior
pituitary → on milk gland cells = milk
production/synthesis.
○ Release of oxytocin from posterior
pituitary → myoepithelial cell contraction
and milk contractions of uterine wall =
milk ejection.
Components of Colostrum
● Alkaline yellow-ish secretion.
● Higher protein and lower lipid + carbohydrate content than break milk.
● Secretory IgAs (and other antibodies):
○ For passive immunity to newborn.
○ From immune cells in stroma.
○ Important for establishing the gut microbiome of infants.

Components of breast milk

 ● Fats (4%) → development of brain, eyes, and nervous system.
● Carbohydrates (7%) → mainly lactose; benets gut microbiota, and aids
calcium absorption.
● Proteins (1%) → essential for growth and development.
● Vitamins and Minerals (0.2%) → vitamin A, C, D, E, riboavin, niacin, etc.
● Prebiotics (0.5-2%) → essential for healthy gut bacteria growth and immune
support.
● Water (86-88%)

Lecture 19: Female Reproductive System III (Uterus)

Uterus
● Body and cervix
● Perimetrium
○ Serosa = mesothelium and thin layer connective tissue.
● Myometrium
● Endometrium

Uterus of Non-menstruating Species

Myometrium
● 3 layers (indistinct):
1. Inner longitudinal
2. Middle circular
3. Outer longitudinal
● Functional syncytium → unit of contraction
comprised of a network of electrically connected
cardiac muscle cells.
 ● During pregnancy:
○ Hypertrophy (50µm - 500µm in length) = the enlargement of an organ or tissue
from the increase in size of its cells.
○ Hyperplasia = enlargement of an organ or tissue caused by an increase in the
reproduction rate of its cells.
○ Differentiation of undifferentiated cells.

Endometrium
● Cyclical changes during menstrual cycle → prepares for implantation of
embryo and subsequent fetal development.
● 2 layers:
○ Functional layer (stratum functionalis)
■ Thickest part closest to lumen
○ Basal layer (stratum basalis)
■ Retained during menstruation
■ Regeneration of functional layer

––→
● Luminal epithelium:
○ Simple columnar
○ Secretory and ciliated cells
● Endometrial stroma:
○ Highly cellular
○ Simple tubular glands (invaginations of the luminal epithelium)
Blastocyst Implantation
● Precise series of events MUST occur.
● Coordinated development of blastocyst and endometrium.
● Uterine epithelial cells play an important role (similar changes across species especially
the initial interaction).

Uterine Luminal Epithelial Cells

● Only cells in body that transform from non-receptive → receptive in short time
frame.
● Simple columnar epithelium:
○ Non-receptive in intestinal epithelial cells.
○ Receptive phenotype.
● Common across majority of species studied.

Uterine Vasculature
● Contains Uterine artery, Arcuate artery, and Radial artery → in the
myometrium
● The Spiral artery extends from the functional layer → basal layer
(endometrium).
○ Highly coiled
○ Important in menstruation
● The Straight artery sits in the basal layer (endometrium).
● Also contains arterioles, capillaries, and venules.
Menstrual cycle
● Functional layer of endometrium
● Regulated by ovarian hormones
● 3 stages (continuum of changes):
1. Menstrual phase
2. Proliferative phase
3. Secretory phase

Proliferative phase (1)

● Follicular phase of ovarian cycle.
● Occurs in Days 5-14.
● Estrogen-dependent
○ Increased estrogen thickens the uterus
lining so that a fertilized egg (embryo) can
implant there.
○ The increased estrogen triggers a decrease
in FSH.
● Changes:
○ Endometrium grows to 3mm in thickness.
○ Regeneration of endometrium →
mitotic gures in epithelium.
○ Spiral arteries → lengthen (not in upper ⅓ of endometrium).
 ○ Glands:
■ Narrow and relatively straight
■ Some glycogen in basal glands

Secretory phase (2)

● Luteal phase of ovarian cycle.
● Occurs in Days 15-26.
● Progesterone (stimulated by LH) = dominant
hormone during this phase to prepare the
corpus luteum and the endometrium for possible
fertilized ovum implantation.
● Endometrium 5-6mm thick.
● Oedematous stroma.
● Changes:
○ Spiral arteries → more coiled and
lengthen to nearly reach surface.
○ Stromal cells
■ Transform into decidual cells
■ Large pale cells
■ Rich in glycogen
○ Glands:
■ Enlarged
■ Corkscrew shape
■ Sacculated appearance (due to glycogen rich secretory products)

Menstrual phase (3)

● Occurs in Days 1-5.
 ● Decline in estrogens and progesterone → degeneration of corpus luteum.
● Periodic contractions of spiral arteries.
○ Ischaemia (inadequate blood supply) of functional layer.
○ Blood flow remains to basal layer.
○ Necrosis (death) of stromal cells.
○ Disruption of surface epithelium and rupture of blood vessels.
● Necrotic tissue separates from the uterus → torn ends of veins, arteries and
glands become exposed.
● Menstrual discharge:
○ 35-50ml
○ Blood, uterine fluid, stromal cells, and epithelial cells of functional layer.
○ Inhibition of blood clotting factors and fibrinolysis (break down clots).

● Proliferative phase (1) begins again with the regeneration of the endometrium.

Endometriosis
● Presence of endometrial tissue outside the uterine cavity.
● Retrograde menstruation.
● 10% women reproductive age.
● Severe pelvic pain, heavy periods, and infertility.
● Current diagnosis = Laparoscopy and Newer ultrasound diagnostics.

Lecture 20: Female Reproductive System IV (Cervix and Vagina)

Cervix
● More connective tissue and less smooth muscle than body of uterus.
● Elastic fibers.
● Large branched glands.
● NO spiral arteries.
 ● Consists of the Ectocervix (outer) and Endocervix (inner).

● Mucosa:
○ No change in thickness during menstrual cycle.
○ Not sloughed off during menstruation.
● Epithelium:
○ Endocervix = simple columnar (continuous with uterus).
○ Ectocervix = stratified squamous (continuous with vagina).

Cervical Mucus
● Produced by glands.
● Provides lubrication of vagina.
 ● Changes during menstrual cycle (under hormonal control).
● In most stages → prevents passage of sperm into the uterus.
● During ovulation:
○ Mucus production is increased 10x.
○ Less viscous with egg white consistency.
○ Favourable for sperm migration.

Nabothian cysts
● = Blocked cervical glands.
● Normal (more with age).

Cervical cancer
● Almost all cases are associated with HPV infection.
● In the past → regular pap-smear testing (every 2 years).
○ Papanicolaou (PAP) staining of cervical cells.
● Now → cervical screening.
○ Detects HPV.
○ More eective → less often screening (every 5
years).

Vagina
● Inner mucosal layer:
○ Non-keratinized stratified squamous epithelium.
○ Connective tissue papillae.
● Muscular layer:
○ Inner circular → outer longitudinal (indistinct
layers).
● Adventitia:
○ Inner dense connective tissue.
○ Outer loose connective tissue.
Vaginal Mucosa
 ● Stratified squamous epithelium (non-keratinized):
○ Contains glycogen (source of energy for lactobacillus → maintains
vaginal pH).
● Lamina propria:
○ Highly cellular with loose connective tissue.
○ In deeper region:
■ Dense submucosa.
■ Some erectile tissue (thin walled blood vessels).

Lecture 21: Fertilization and Pre-implantation Embryo Development

Oocyte
● 1 ovulated per cycle in humans → secondary oocyte.
○ Meiosis is resumed due to LH surge.
○ 24 hours prior to ovulation.
○ Viable for 24 hours.

(GVBD = germinal vesicle breakdown)

Sperm
● Millions per ejaculate.
● Deposited in the anterior vagina → not exposed to vaginal acidic
environment, avoids immune cells in vagina.
● Can survive 5 days in female reproductive tract.

Sperm meets Oocyte

● Sperm move into the uterus by active swimming, chemotaxis, and thermotaxis to locate
the oocyte in the fallopian tube.
1. Sperm in the vagina move to oviduct by:
○ Active swimming.
○ Passive drag by female reproductive tract muscle contraction.
2. Sperm reach the storage site (reservoir of isthmus) of oviduct → undergoes
capacitation.
3. Sperm then move towards the oocyte in the ampulla by:
○ Thermotaxis = ovulation-dependent temperature gradient.
○ Chemotaxis = chemoattractants secreted by oocyte and surrounding cumulus
cells.

Sequence of events for successful fertilization

1. Sperm capacitation
2. Penetration of corona radiata
3. Penetration of zona pellucida
4. Fusion of sperm and oocyte membranes

Sperm Capacitation
● Sperm leaving the testis are morphologically complete but lack the capacity to fertilize
the oocyte (immotile and contain remnants of the cytosolic bridges that synchronize
spermatogenic cells until spermiation).
● In the epididymis, spermatozoa:
○ Acquire motility characteristics
○ Lose the cytoplasm droplet
○ Under some final chromatin condensation
● In the epididymis, capacitation is inhibited by adherence of decapacitation factors.
○ In female reproductive tract, inhibitors of capacitation is removed.

Sequence of surface changes rendering spermatozoa able to fertilize the oocyte

● Maturation in epididymis:
○ Adherence of proteins involved in sperm-zona binding and surface stabilization.
● At ejaculation = sperm is mixed with seminal plasma.
○ Adherence of glycoproteins.
○ Proteins in seminal fluid prevent capacitation.
● In the upper female reproductive tract:
○ Removal of decapacitation factors.
 ○ Redistribution of proteins to allow binding of zona pellucida proteins.
Sperm Capacitation in oviduct
● Tyrosine kinase activation (increased tyrosine phosphorylation).
○ Increased glycolysis → ATP production.
○ Hyperactivated motility:
■ Sudden influx of Ca2+ through CatSper channels.
■ Tail becomes more active and bend more forcefully.
■ Faster movement.

Sperm are guided to the oocyte after capacitation

● Sperm undergo capacitation in the reservoir.
● After capacitation:
○ Sperm acquire motility pattern known as ‘hyperactive motility’.
○ Sperm become detached from the epithelium.
● Sperm are then guided to the oocyte by Thermotaxis and Chemotaxis.

Sperm Thermotaxis
● Sperm can respond to temperature differences <0.0006 ºC.
● Temperature gradient is generated in the oviduct during ovulation.
● Sperm swim to a warmer temperature by actively changing their swimming direction by
modulating the frequency of turns and hyperactivation events.
● Only capacitated sperm can respond to temperature gradients.
● Thermosensors in sperm:
○ Opsins (G-protein coupled receptors)
○ TRPV1 ion channels:
■ Cause influx of calcium
■ Guides direction of swimming

Sperm penetrate corona radiata

● Ovulated oocytes = surrounded by cumulus cells held together by extracellular matrix
rich in hyaluronan.
○ Acrosomes contain hyaluronidase.
● Some capacitated sperm undergo premature acrosome reaction to break apart cumulus
and enable other sperm to reach the zona for binding.
● Cumulus cells release progesterone that can trigger the acrosome reaction.
● Cumulus controls sperm – zona pellucida encounters.

Acrosome reaction
1. Sperm bind to proteins on the zona pellucida.
2. A secretory vesicle (the acrosome) is fused with the sperm plasma membrane.
3. The acrosomal contents are released.
4. Exposure of the inner membrane of the acrosomal vesicle.
Sperm penetration of the zona pellucida
● Acrosome enzymes on inner membrane (especially acrosin) allows for the digestion of
zona pellucida in a small area to allow for sperm entry.
● Whiplash forward propulsion of hyperactivated tail.
● Penetration of the zona pellucida takes 5-20 mins.
● Acrosome reacted sperm have a very short lifespan.

Fusion of sperm and egg

1. Sperm head binds to oolemma via fertilin (ADAMs) interaction with integrins and CD9.
2. Sperm head fuses with oocyte
○ Involves IZUMO1 on sperm and JUNO on egg.
3. Sperm head taken into oocyte
○ Tail, mitochondria, and plasma membrane is left behind.

Sperm fusion causes intracellular Ca2+ oscillations in the oocyte

1. Fusion
2. PLCzeta released from sperm into oocyte.
3. Increase in intracellular IP3.
4. Increase in intracellular Ca2+.
5. Oscillations in intracellular Ca2+.
6. Cell cycle resumption.
7. Cortical granule exocytosis.
8. Block to polyspermy.

Zygote formation
● Male pronucleus is formed from sperm nucleus.
● Second polar body forms at the completion of meiosis II.
● Female pronucleus forms.
● The 2 pronuclei fuse (~20 hours after fertilization).
● Zygote undergoes rst mitotic cleavage → give rise to 2-cell stage embryo.
Summary of fertilization
1. Capacitation
2. Acrosome reaction
3. Fusion of sperm membrane and oolemma
4. Cell cycle resumption
5. Zygote formation

Fertilization in assisted reproduction

● Intrafallopian tube insemination / artificial insemination.
● In vitro fertilization (IVF): sperm and oocytes are incubated together in a dish.
● Intracytoplasmic sperm injection (ICSI).

Pre-implantation stages of embryo development (Days 0-6)

● Repeated mitotic divisions:
Compaction leads to formation of 2 cell types

1.

Totipotent cells
○ Blastomeres polarize along the axis of cell contact.
○ Outward apical domains.
○ Inward-facing basolateral domains.

2. Pluripotent cells
○ Radial cleavage → 2 polar cells.
○ Tangential cleavage → 1 polar cell + 1 non-polar cell.

Blastocyst expansion
Blastocyst hatching is required for implantation
● Rupture of zona:
1. Mechanical pressure → zona thinning
2. Chemical digestion:
○ Proteases
○ Hole in zona
● Escape from zona
3. Embryo movements
○ Cell migration
○ Expansion/collapse of cavity

Assisted Reproductive Technologies (ART)

● Only 23% of ART treatments result in a clinical pregnancy.
● Poor embryo development in vitro.
● Implantation failure.

Growth factors are not added to embryo culture media

● No serum, simple media.
● Maternal growth factors are absent.
● Large volume of media means autocrine growth factors are diluted.
○ Decreased blastocyst development / implantation.

In vitro embryo culture and assisted conception

● Absence of signaling molecules and increased ROS → Suboptimal embryo
culture medium → Poor in vitro development → Low rates of implantation and
pregnancy.
● Addition of exogenous signaling molecules and antioxidants → Optimal
embryo culture medium → Better in vitro development → Increased rates of
implantation and pregnancy.
Lecture 22: Fertilization and Pre-implantation Embryo Development

Implantation
● Precise series of events – maternal and fetal tissues.
● Uterine glands – full of secretory products.
● Aim to access maternal blood supply – forms placenta.

Invasion of Endometrium
● Trophoblast cells → secrete hCG.
● Rapid proliferation.
● Cytotrophoblast:
○ Mitotically active
○ Inner cell layer
○ Production of cells that fuse with syncytiotrophoblast.
● Syncytiotrophoblast:
○ Not mitotically active
○ Multinucleated
○ Active invasion
● Syncytiotrophoblast invade into maternal blood vessels.
● Lacunae form.

Day 11-12 development

● Closing plug is formed.
● Implanted embryo within wall of endometrium.

Chorionic Villi form

● Proliferation of cytotrophoblast.
● Growth of chorionic mesoderm.
● Blood vessel development
● Chorionic villi → primary, secondary, and tertiary.

Primary Chorionic Villi

● Around day 13 post-fertilization.
● Cords or masses of cytotrophoblasts grow into lacunae within syncytiotrophoblast.

Secondary Chorionic Villi

● Day 16 development.
● Central core mesenchyme.
● Inner layer = cytotrophoblast.
● Outer layer = syncytiotrophoblast.
● Primary villi invade by loose connective tissue from chorion.
 ● Entire surface of chorionic sac.

Tertiary Chorionic Villi

● End of 3rd week development.
● Embryonic blood vessels grow into
secondary villi.
● Early Tertiary Villi histology:

● Mature Tertiary Villi histology:

(C = cytotrophoblast, S = syncytiotrophoblast, PM = placenta macrophage, SK = syncytial knots,
IS = intervillous space, CV = chorionic villi, UV = uterine vessel).

Maternal Component of Placenta – Decidualization

● Occurs after implantation of blastocyst (8-10 days of embryo development).
● Stromal cells → become large round decidual cell.

Regions of Decidua
● Decidua basalis = endometrium below implantation site.
● Decidua capsularis = between implantation site and lumen
● Decidua parietalis = remaining endometrium.

Decidualization
● By end of 3rd month gestation → decidua capsularis fuses with decidua
parietalis of opposite wall.
○ Obliteration of uterine cavity
● All but the deepest layers of the endometrium form the decidua.
● Decidua shed with placenta at birth.
Cytotrophoblastic shell
● = Complete shell around syncytiotrophoblast.
○ Attaches to endometrium.
● Maternal blood vessels communicate through the shell.

Growth of Villi
● Occurs continuously throughout pregnancy.
● Floating villi = free in intervillous space.
● Main stem villi or anchoring villi = grow into maternal side of placenta (via basal plate).

Chorionic Villi
● Initially villi cover the entire surface.
● Smooth area (smooth chorion) develops at approx 8 weeks of gestation.
● Chorionic plate.

During pregnancy
● Villi mature (smaller in diameter).
● Cytotrophoblast becomes discontinuous.
● Syncytial knots appear (syncytiotrophoblast nuclei gathered in clusters).
Mature placenta
● Basal plate (from decidual basalis).
● Chorionic plate (from embryological origin).
● Rapid growth villous chorion.
● Cotyledons:
○ Divide fetal part of placenta.
○ 15-25.

Blood supply to placenta

● Spiral arteries are higher pressure than intervillous space.
○ Arterial blood directed deep into intervillous space.
○ Blood flows over surface of villi into the endometrial veins.
Placental barrier
● Function: separation of maternal and fetal blood.
● Very thin by 4th month.
○ Allows for exchange of products across the placenta.
● Similar to air-blood barrier.
● Minimal thickness in:
○ Syncytiotrophoblast.
○ Thin cytotrophoblast.
○ Basal lamina of trophoblast.
○ Mesenchymal tissue of villus.
○ Basal lamina of endothelium.
○ Endothelium.

Functions of Placenta
● Metabolism → nutrients and energy for developing
embryo.
● Transport:
○ Nutrients, ions, water, macromolecules, drugs, hormones, etc.
○ Via diffusion, active transport, passive transporters, and pinocytosis.
● Barrier function.
● Immunological function.
● Endocrine functions.

Placenta – Endocrine organ

● Progesterone and estrogens:
 ○ Placenta takes over from corpus luteum (at 8 weeks of gestation).
○ Adrenal cortex produces androgens (precursors for estrogen production).
● Human chorionic gonadotropins:
○ Produced from 6 days post-fertilization.
○ Maintains the corpus luteum, the endometrium, and pregnancy.
■ 85% homology to LH.
○ Used for home pregnancy tests.
● Human chorionic somatomammotropin:
○ Human placental lactogen.
○ Secreted by syncytiotrophoblasts.
○ Related to human growth hormone.
○ Regulates glucose metabolism.
○ Stimulates mammary duct proliferation in breast.
● Relaxin:
○ From decidual cells.
○ Softening of cervix and pelvic ligaments.
● Other hormones secreted by the placenta → IGF-I, IGF-II, Endothelial Growth
Factor, and Leptin.

Placental problems
● Placenta previa = placenta covers internal os of cervix.
● Placenta abruption = placenta comes away from uterine wall.

Ple-Eclampsia
● Pregnancy induced hypertension + proteinuria.
● Intrauterine growth restriction.
● HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets).
● Treatment → delivery of placenta.
● Unknown cause → problems with endometrial blood vessel development.