Female Reproductive System

The Reproductive System of a Human Female consists of

paired internal ovaries and paired uterine tubes/oviducts
that provide a passageway from the ovaries to the uterus.
Adjacent to the uterus and separated by cervix is a vagina
The individual organs of the female reproductive system
perform numerous important functions, including secreting
female sex hormones (estrogen and progesterone),
producing ova, providing suitable environment for
fertilization of the oocyte, transporting and implanting
blastocydt, development of the fetus during pregnancy, and
nutrition of the newborn

OVARIES
• Flattened, ovoid or almond-shaped structure located deep in the pelvic cavity.
• One section of the ovary is attached to the broad ligament by a peritoneal fold
called Mesovarium; and, another section to the uterine wall by an ovarian ligament.
• Ovarian surface is covered by a single layer of cuboidal cells called the germinal
epithelium which overlies the dense irregular connective tissue tunica albuginea
Ovarian surface/ germinal epithelium, continuous with the mesothelium and overlying
a dense connective tissue capsule, the tunica albuginea like that of the testis.

• Located inferior to the tunica albuginea is the cortex of the ovary. Deep to the
ovarian cortex is the highly vascularized, fibrous connective tissue core of the ovary,
the medulla
• Cortex – A region filled with a highly cellular connective tissue stroma and many
ovarian follicles
• Medulla – internal part containing loose connective tissue and blood vessels
There is no distinct boundary line between the cortex and medulla, and these two regions blend together
Ovarian Follicle – consists of an oocyte surrounded by one or more layers of epithelial cells.
• The cortex is normally filled with numerous ovarian follicles in
various stages of development
• Corpus Luteum of an ovulated follicle, the source of the
hormone progesterone
• Corpus Albicans of a degenerated corpus luteum

PRIMORDIAL FOLLICLE
• Primary Oocyte surrounded by a single layer of flattened
follicular cells
• Formed during the fetal life
• Found in the superficial areas of the cortex
• Oocyte is at the prophase stage
• Stimulated by FSH to undergo maturation
 Stages of Ovarian Follicles, form primordial to mature
First Image:
The cortical region of the ovary is surrounded by the surface epithelium, usually
cuboidal cells. This layers is sometimes called the germinal epithelium because of an
early erroneous view that it was the source of oogonia precursor cells. Underlying
the epithelium is a connective tissue layer, tunica albuginea.
Groups of primordial follicles, each formed by an oocyte (O) surrounded by a layer of
flat epithelial follicular cells,
Outside: Stromal Cells

• Big nucleus, dispersed chromatin

• Presence of Zona Pellucida, a layer of extracellular material consisting of
glycoproteins secreted by oocytes.
• Unilaminar PF: oocyte surrounded by a single layer of simple cuboidal
epithelium
• Multilaminar/Multilayered PF: oocytes surrounded by stratified cuboidal
epithelium, termed as granulosa cells

These Glycoproteins bind proteins on the surfaces of the sperm and induce
acrosomal activation. For Sperm Binding and fertilization.
Granulosa cells (follicle cells but not flattened) – estrogen production
Zona Pellucida components glycoproteins ZP3 and ZP4 are important sperm
receptors, binding specific proteins on the sperm surface and inducing acrosomal
activation
Stroma  Theca (follicular theca) ( theca – outer covering)
Theca Interna – vascularized; steroid producing cells – estrogen and
androstenedione
Theca Externa – fibrous with fibroblasts and smooth muscles
As the primary follicles grow, they move deeper in the ovarian cortex
Cells secrete follicular fluid – antrum

SECONDARY/ANTRAL FOLLICLE
• Vesicular Follicle
• Presence of follicular antrum
• Follicular antrum – a cavity or space due to
coalescence of follicular fluid around granulosa cells
• Granulosa cells start to form a crown around the oocyte (corona radiata)
• First Meiotic division completed
Follicular antrum – a cavity or space due to coalescence of follicular fluid around
granulosa cells
• Theca interna – secretes estrogen; ligher staining than theca externa due to the
presence of lipid droplets /steroid hormones
• Theca externa – layer containing smooth muscles and fibroblast
• Basement Membrane – separates Theca interna from granulosa cells
Always look for the antrum/antral cavity
MATURE/ GRAAFIAN FOLLICLE
• AKA Preovulatory Follicle
• Contains Secondary Oocyte and commences the second meiotic division
• Granulosa cells form a crown around the oocyte (corona radiata)
• Forms cumulus oophorus: thickened area of granulosa cells forming a small
hillock that surrounds the oocyte

Named after a reproductive biologist Regnier De Graaf

Note: Look for markedly large antrum (continuous) and Eccentric oocyte; Very thick
thecal layers; Superficially located ( at the ovarian surface); forms a bulge at the ovary surface visible with ultrasound
imaging; granulosa layers are thinner because it cells do not multiply in proportion to the growth of the antrum.; thick
thecal layers
On ovulation: oocyte, Zona pellucida and corona radiata are released
Corona radiata accompany the oocyte when it leaves the ovary at ovulation

Atresia involves apoptosis and detachment of the granulosa cells, autolysis of the
oocyte, and collapse of the zona pellucida.
Ovulation: hormone-stimulated process by which the oocyte is released from the
ovary. Ovulation normally occurs midway through the menstrual cycle (14th day
of a typical 28th day cycle)
Just before ovulation, the oocyte completes the first meiosis.
The oocyte, corona radiata along with follicular fluid are expelled by local smooth
muscle contractions.
The ovulated secondary oocytes adheres closely loosely to the ovary surface in the
viscous follicular fluid and is drawn into the opening of the uterine tube where fertilization may occur.
If not fertilized within 24 hours, the secondary oocyte begins to degenerate.
Cells of the ovulated follicle that remain in the ovary redifferentiate under the influence of LH and give rise to corpus
luteum.

OOGENESIS
Oogenesis begins in the female fetus, with primary oocytes arresting at prophase 1 in primordial follicles, which remain
inactive during childhood. At puberty, a population of primordial follicles begins to develop each month. Typically one
per month produces a female gamete ( secondary oocyte)
Many primary oocytes are lost through a slow, continuous degenerative process called atresia which continues through
a woman’s reproductive life.
at 2 month ermbryo – 600,000 oogonia
At 5th month embryo – 7 million oogonia
Oogonia – Primary oocytes
Primary oocytes + follicular cells
At 7th month – most oogonia have transformed into primary oocytes
At puberty 300,000 oocytes
Only one oocyte resumes meiosis with ovulation during each menstrual cycle ( average 28 days) and the reproductive life
of woman lasts about 30-40 years - only about 450 oocytes are liberated from ovaries by ovulation. All others
degenerate through atresia.
FSH – follicular growth 44

CORPUS LUTEUM
• AKA Yellowish Body
• Large, temporary endocrine gland form after reorganization of theca interna and granulosa cells of ovulated
follicle
 • Granulosa lutein cells – undergo significant hypertrophy, producing most of
the corpus luteum’s increased size, and begin producing progesterone
• Theca lutein cells – theca interna that slightly increase in size, and darker
staining than the granulosa lutein cells, and continue to produce estrogen; progesterone

Cells of the granulosa and theca interna become reorgranized under the influence
of the LH and their names are changed
Ovulation is followed immediately by the collapse and folding of the granulosa
and thecal layers of the follicle’s wall, and blood from disrupted capillaries
typically accumulates as a clot in the former antrum. The granulosa is now
invaded by capillaries.
Theca lutein cells are half the size of the granulosa lutein cells and are typically
aggregated in the folds of the wall of the corpus luteum, which, like all endocrine
glands, becomes well vascularized. LH causes these cells to produce large amounts of
progesterone as well as androstenedione ( Junquiera)
Zona granulosa is now invaded with capillaries. Capillaries V
Characterized by folds of the former granulosa that collapses as theca externa contracts at ovulation. The former antrum
often contains blood clot from vessels in the thecal layers disrupted during evaluation.

GL – progesterone
TL – Estrogen; dark staining; derived from theca interna; typically located
within the folds.
Regresses 12-14 days without fertilization; 10 -12 days without further LH
stimulation in the absence of pregnancy – undergo apoptosis. A consequence
of the decreased secretion of progesterone is menstruation, the shedding of
part of the uterine mucosa. Estrogen produced by the corpus luteum
inhibits the FSH release from the pituitary. However, after the corpus luteum
degenerates, the blood steroid concentration decreases and FSH secretion
increases again, stimulating the growth of another group of follicles and beginning the next menstrual cycle.
Corpus luteum of menstruation
Remnants from its regression are phagocytosed by macrophages, after which fibroblasts invade the area and produce a
scar of dense connective tissue called corpus albicans. ( white body)
Corpus luteum secretes progesterone and estrogen, a steroid hormone. Thus it appears vacuolated ( with lipid
vacuoles). In contrast to corpus albicans, which is a scar of dense connective tissue

CORPUS ALBICANS
• Inactive fibrous tissue mass that forms following the involution of a corpus
luteum
• The scar of connective tissue that forms at the site of corpus luteum after its
involution.
• It contains mostly collagen, few fibroblasts
• Macrophages phagocytse degenerated secreting cells

Involution (decline in function; decrease in size) Involution of corpus luteum does not
involve atresia
Note: less to non-vacuolated; smoother than corpus luteum
Gradually becomes smaller and lost in the ovarian stroma
UTERINE (FALLOPIAN) TUBE
• AKA Oviduct
• Extends from the ovaries to the Uterus
• Divided into 4 continuous regions.
1. Infundibulum – close to the ovary, funnel shaped with fingerlike extensions called fimbriae (next to the ovary)
2. Ampulla – widest and longest portion; continuous w/ the infundibulum; expanded region where fertilization
normally occurs.
3. Isthmus- short and narrow; joins the uterine tube to the uterus
4. Interstitial (intramural/ uterine) region – passes through the thick uterine wall to open into the uterine cavity

• Carry ova from the surface of the ovaries to the uterine cavity and are
also the site of fertilization by spermatozoa (Ampulla)
• Lining: Simple Columnar Epithelium, Ciliated
• Secretory PEG Cells: Simple Columnar Epithelium, Non-Ciliated
• Mucosa: Thrown into labyrinth of branching folds; most prominent in the
ampulla
• Muscularis: ICOL orientation

Muscularis: Thinner than uterine wall

Mucosa: Mucosal Folds becomes smaller in the regions closer to the uterus
and are absent in the intramural part.
Muscularis thickens as it gets closer to the uterus, while the mucosal folds
decrease in size.
The epithelium contains two interspersed, functionally important cell types
Ciliated Cells – ciliary movements; sweep fluid toward the uterus; sweep
egg cell toward the uterus
Secretory PEG cells – nonciliated and often darker staining, often with an
apical bulge into the lumen. Secrete glycoproteins of a nutritive mucus film
that covers the epithelium
The secretion covering the mucosa has nutritive and protective functions for both the oocyte and the sperm,
including capacitation factors that activate sperm and make those cells able to fertilize an oocyte.
Secretions are protective and nutrient functions for both ovum and the sperm

FALLOPIAN TUBE VS SEMINAL VESICLE

Fallopian Tubes
Lining: Simple Columnar Epithelium, Ciliated +
Secretory PEG cells(nonciliated)
Mucosa: folded, labyrinth appearance (you can trace
the path from lumen to the muscularis)

Muscularis: ICOL
Seminal Vesicles
Lining: Pseudostratified columnar epithelium, nonciliated
Mucosa: highly folded; finer; Honeycomb appearance ( the path is always a “dead-end”)
Muscularis: ICOL
UTERUS
• Pear-shaped organ with a thick wall.
• The body or corpus is the major portion of the uterus (largest)
• The rounded upper portion of the uterus that extends above the entrance
of the uterine tubes is the fundus.
• The lower, narrower, and terminal portion of the uterus below the body
or corpus region is the cervix (lower cylindrical structure)

The cervix protrudes and opens into the vagina

The cervical canal has constricted openings at each end: the internal os (opens to the main uterine lumen); and the
external os (open to the vagina)

The walls of the uterus have three layers:

1. an outer perimetrium (serosa or adventitia)
2. a thick middle layer myometrium that consist of highly
vascularized smooth muscle
3. an inner endometrium lined by
simple columnar epithelium

Adventitia in some parts, but largely a serosa (covered by

mesothelium) Mesothelium: epithelium that lines the pleura,
peritoneum, pericardium
Perimetrium – composed of a single layer of mesothelial cells; very thin outer serosa which is the peritoneal layer of the
broad ligament

UTERUS – ENDOMETRIUM
Lining: Simple Columnar Epithelium, ciliated with Tubular Uterine Glands
Lamina Propria: Type III Collagen Fibers
Subdivided into 2 layers
1. (Luminal/Functional) Stratum Functionalis
- Dramatic changes during menstrual cycle; shed off during menstruation
- Spongier lamina propria, rich in ground substance, includes most of the length of the glands
• a. Stratum Spongiosum – Broad intermediate layer characterized by “spongy” stroma
• b. Stratum Compactum – thinner superficial layer
2. (Basal) Stratum Basalis
- Deepest Layer adjacent to the myometrium. It exhibits little change during menstrual cycle. It is not shed during
menstruation.
- Contains highly cellular lamina propria and deep basal ends of uterine glands

Arcuate Arteries in the middle layers of the myometrium send two sets of smaller arteries into the endometrium
Straight arteries – supply the basal layer
Spiral Arteries – long, that extend farther and bring blood throughout the functional layer. Spiral Arteries branch with
numerous arterioles supplying a rich, superficial capillary bed that includes many dilated, thin walled vascular lacunae
drained by venules.
Menstrual Cycle
(Explain)
GRH – FSH and LH --….. ESTROGEN And PROGESTERONE – promote growth and development of the
endometrial functional layer. w/o fertilization, the tissue sloughs off as the menstrual flow (first day of which is taken
to mark day 1 of both the ovarian and uterine cycle)
UTERUS – MYOMETRIUM
Thickest tunic of the uterus
Thick smooth muscle wall which expands greatly during pregnancy and
provides protection for the fetus and a mechanism for the expulsion of fetus
during parturition.
Layers of Myometrium
1. Stratum Subvasculare – inner longitudinal smooth muscle layer;
adjacent to endometrium
2. Stratum Vasculare – middle circular or spirally arranged muscle fibers;
thickest and forms bulk of the myometrium
3. Stratum Supravasculare – outer layer; both circular and longitudinal
fibers

Parturition- the act of giving birth

Myometrium – may undergo hypertrophy (increase in smooth muscle cell size) , and to some extent hyperplasia(
increase in the number of smooth muscle cells) in response to Estrogen
Connective Tissue – Embryonic Connective Tissue (Mesenchymal Cell)

Menstrual Phase
Day 1 of the menstrual cycle
Last 3-4 days
Proliferative Phase/ Follicular/ Estrogenic
8-10 days (5 -14)
After the menstrual phase
Coincides with the rapid growth of ovarian follicles growing as vesicular
follicles
Theca Interna – Secrete Estrogen
Estrogen act on the endometrium – regeneration of the functional layer
lost during menstruation; endometrial lining – simple columnar
epithelium; spiral arteries lengthen as the functional layer is reestablished
and grows
Uterine Glands: Straight Tubules
Secretory Phase/Luteal Phase
Begins at ovulation
Lasts about 14 days
Starts as a result of progesterone secreted by the corpus luteum
Progesterone stimulates epithelial cells of the uterine glands to secrete and
accumulate glycogen – dilating the glandular lumens and causing the glands
to become coiled
The endometrium reaches its maximum thickness during the secretory
phase as a result of accumulation of secretions in the stroma
If fertilization occurred during the day after ovulation, the embryo has
been transported to the uterus by about 5 days later and now attaches to the
uterine epithelium when endometrial thickness and sensory activity are
optimal for embryonic implantation and nutrition.
The major nutrient source for the embryo before and during implantation is the uterine secretion. (Promoted by
Progesterone)
Progesterone also inhibits strong contractions of the myometrium that might interfere with embryo implantation
PROLIFERATIVE ENDOMETRIUM
Proliferative Phase: Day 5 to 14
- High Estrogen
- Endometrial stroma proliferates becoming thicker and vascular
- Glandular Epithelium: Low columnar epithelium with round nuclei
(basally located)
Early Proliferative
Uterine Glands – fairly sparse and straight
Late Proliferative
Uterine Glands – becomes coiled and tightly packed

Proliferative Endometrium = straight glands

F – stratum functionalis
B – stratum basalis
SECRETORY ENDOMETRIUM
- Marked by Ovulation
- “Progestational Stage”
- Secretory Phase: Day 15-28
- Active Corpus Luteum= High Progesterone
Early Secretory
- Uterine Glands: Convoluted/Coiled
- Glandular Cells: presence of subnuclear vacuoles
Late Secretory
- Uterine Glands: Sawtooth appearance
- Glandular Cells: basally located nuclei, with luminal vacuoles

Progesterone = stimulates glandular cells to secrete Glycogen, an important source of nutrition for the fertilized
ovum
Subnuclear vacuoles (V); due to accumulated glycogen

EARLY VS LATE SECRETORY ENDOMETRIUM

CERVIX
- Lower part of the uterus that projects into the vaginal canal as portiovaginalis
- Links uterine cavity with the vagina
- Unlike the functionalis layer of the uterine endometrium, the cervical mucosa undergoes minimal changes and is
not shed during menstruation.
- Contain numerous branched cervical mucus-type glands
 - More collagenous tissues, few smooth muscle fibers
Endocervix
- Lining: Simple Columnar Epithelium with thick lamina propria
- Lacks spiral arteries; does not change its 2-3mm thickness
- Does not shed during menstruation
- Endocervical glands: mucus secreting; branched tubular gland
- Estrogen – stimulates the gland to secrete thin, watery mucus
- Progesterone – stimulates the gland to secrete thick, viscid mucus
Ectocervix
Lining: Stratified Squamous, Non-keratinized
Junction / Transition Zone/Transformation Zone
- Prone to malignancy(neoplasia); located near/on the external os

- The cervix differs histologically from the rest of the uterus

- During Ovulation, admit spermatozoa to the genital tract at the time
when fertilization is possible
- In pregnancy, protects the uterus and upper tract from bacterial invasion
- During parturition( act of giving birth), permit passage of the fetus
- A narrow endocervical canal passes through the cervix.
- Opening of this cervical canal that communicates with the uterus is the
internal os
- Opening of this cervical canal that communicates with the vagina is the
external os

VAGINA
Lining
- Stratified Squamous Non-keratinizing Epithelium
Lamina Propria
- Rich in Elastic Fibers, small blood vessels, devoid of glands
Muscularis
- ICOL orientation

No glands in its wall in contrast to ectocervix; lubricated by mucus

produced by the cervical glands of the cervix.
Superficial cells produce glycogen (Stimulated by Estrogens) to be
metabolized into lactic acid (low pH) which inhibits growth of pathogenic
microbes
Inner mucosa – lined by stratified squamous epithelium nonkeratinizing
Middle muscular layer
Outer connective tissue –adventitia
Mucus in the vagina is produced by the cervical gland and vestibular glands of Bartholin (homologous to male
bulbourethral gland)

EXTERNAL GENITALIA
The female external genitalia or vulva include several structures, all covered with stratified squamous epithelium,
nonkeratinizing
1. Vestibule – a space whose wall includes the tubulo-acinar vestibular glands
2. Paired Labia Minora – folds of skin lacking hair follicles but with numerous sebaceous glands
3. Paired Labia Majora – homologous and histologically similar to the skin of the scrotum
4. Clitoris – erectile structure homologous to the penis with paired corpora cavernosa
 UMBILICAL CORD
2 Arteries (UA) – carry deoxygenated blood away from the fetal heart and to
the placenta
1 Vein (UV) – carry oxygenated blood
Cells:
Mesenchymal Cells
Surface Amnion (Am)
Fibroblast (F)
Connective Tissue:
- Mucous Tissue, aka Wharton’s Jelly (W)
- principal component of the umbilical cord
- Ground Substance: Hyaluronic acid

EARLY PLACENTA
- Composed both maternal and fetal tissues
Decidua (D) Derived from the maternal endometrial lining
Lacuna (L) where maternal blood flows
Chorionic Villi (V) dilated fetal capillaries

Primitive Mesenchyme(M)
Intermediate Trophoblast (I)
Differentiates into:
1. Cytotrophoblast (c)
-inner layer
- Langhan’s layer of pale Mononuclear cells
2. Syncytiotrophoblast (S)
- Outer layer, fused cytotrophoblast forming a multinucleated syncytium of cells; darker layer
Secretes hCG, human placental lactogen, progesterone, estrogen, etc.

Mesenchyme – found within the villous core

TERM PLACENTA
- Many smaller chorionic villi (V)
- Presence of syncytial knots (K)
- Many capillaries (C) within the villous core than that of early placenta

Syncytial knots- aggregated clusters of syncytiotrophoblast nuclei)

Early placenta: usually has mesenchyme only
Early Placenta: Larger Villi; mesenchymal villous core, No syncytial knots
Term Placenta: Smaller Villi, capillaries on villous core, with syncytial
knots

RESTING MAMMARY GLAND

Mammary Glands
- Apocrine Secretion; modified apocrine sweat glands
- Compound Tubuloalveolar
- Secretes MILK
- Alveoli: simple cuboidal epithelium
- With myoepithelial cells that are stellate in shape
 - Characteristics:
- Abundant Adipose Tissue (A-
- Small acini.alveoli (Al) surrounded by fibrous CT
- Present in mature and non-pregnant women

Myoepithelial cells (arrow)

Characteristics of Resting Mammary Gland
The mammary gland, in both sexes, develop in the same manner and are of the
same structure until puberty where changes brought about by interplay of
hormones cause further development and structural changes within the gland.

ACTIVATE/LACTATING MAMMARY GLAND

- Compound alveolar/saccular
- Undergo growth during pregnancy as a result of estrogen, progesterone,
prolactin, and human placental lactogen.
- Lobules (Lo) become much larger and more extensively branched
- Appear like thyroid follicles
- Acini begin to accumulate milk
- Colostrum – milk + lipids; makes acini dilate; eosinophilic materials rich
in IgA and vitamin A; laxative substances and maternal antibodies

Stoma become less prominent; loose connective tissue becomes infiltrated with
lymphocytes (L) and plasma cells (P)
Active – acini begin to accumulate with milk ( arrow, Left picture)
Lactating – acini distended with milk ( Right Picture)

LACTATING MAMMARY GLAND VS THYROID FOLLICLE

Lining: Simple Cuboidal Epithelium
Lactating: Less Homogenous; Eosinophilic material
within acinar lumen - milk/colostrum (lipids)
Thyroid follicle: More homogenous; smoother
appearance; eosinophilic material within follicular
lumen – colloid (thyroid hormones)