Embryology

Reproductive System

human body contains 23 pairs of Chromosomes, adding to a total of 46 chromosomes.

-Male gonad is the Testis

-Female gonad is the Ovaries
Gonads produce highly specialized cells known as gametes
-Male gametes are called Spermatozoa (Spermatozoon)
-Female gametes are referred to as Ova (Ovum)

Gametogenesis- process of meiosis and cytodifferentiation that converts the primordial germ cells
into male and female gametes.
-Male "" = Spermatogenesis and commences at puberty, then is continuous as waves of
spermatozoa are produced throughout life.
-Female "" = Oogenesis and is initiated in the fetus but is immediately arrested and doesn't
commence until puberty. then single oocyte (usually) in alternating ovaries responds to a surge of
gonadotropins 1x/month until menopause (40-50 y.o)
-Gonadotropins- protein hormones secreted by gonadotrope cells of the pituitary gland

Female Reproductive System

Major Organs:
1. Uterus-(womb) is a hollow pear-shaped organ woman's lower abdomen btw bladder and
rectum.
2. Ovaries- ovum producing reproductive organ
3. Fallopian Tubes-(Oviducts)-two very fine tubes lined with ciliated epithelia that lead
from the ovaries of a female into the uterus.
4. Vagina-a fibromuscular tubular tract leading from the uterus to the exterior of the body
in females.

Sections of the Uterus

1. Fundus- Superior wall of the Uterus, opposite to the cervix
2. Cervix(Cx)- the lower, narrow portion of the uterus where joins w top end of the vagina.
a) Internal Orifice (Internal Os)-the interior narrowing of cervix
b) External Orifice (External Os)-the exterior opening of cervix, it is a small,
depressed, somewhat circular aperture on the rounded extremity of the vaginal portion of the cervix.
cervical cavity communicates w vagina cavity through this aperture
3. Body of the Uterus-(cavity of the body)the triangular-shaped cavity within the Uterus,
and has two different segments.
a) Lower Uterine Segment- Inferior half of the uterine cavity which joins with
the cervical canal.
b) Upper Uterine Segment- superior half of the uterine cavity, this is where the
placenta should attach
4. Uterine Wall- consists of 3 different layers
a) Endometrium-the inner most layer of the uterine wall. **********
 b) Myometrium- middle
c) Perimetrium- outer most

Endometrium
-contains glands and blood vessels that are responsive to both the hormones Estrogen and
Progesterone
-thickens during the Proliferate Phase of Menses due to the release of the hormone
Estrogen, this helps make a cushion for successful implantation of the egg into the Endometrium. A
thick endometrial layer will keep the zygote from falling off.
-In the case of fertilization, the placenta will continue to secrete the hormone Progesterone
in order to maintain the state of the endometrium.

Sections of the Fallopian Tubes

1. Infundibulum with Fimbria- when ovulation is about to occur, the sex hormones activate
the fimbriae, causing it to hit the ovary in a gentle, sweeping motion. Once the Oocyte is released from
the ovary into the peritoneal cavity, the cilia of the fimbriae sweep the Ovum into the Fallopian Tube.
2. Ampulla- *This is where fertilization should occur.* This is the dilated portion of the
Fallopian Tube in between the Infundibulum and the Isthmus. (The literal definition of Ampulla is
simply the dilated region of a tube.)
3. Isthmus- the narrow elongated portion of the Fallopian Tube that connects the Ampulla
and the Intramural Part. The fertilized egg will travel through this segment before implanting itself to
the endometrium.
4. Intramural Part- this is the part of the tube that is the short segment that passes through
the thick myometrium of the uterus and opens via that uterine ostium into the uterine cavity.

Ovaries
-contains eggs at various stages of development
-prior to puberty the two ovaries are smooth almond shaped organs, after puberty, however,
due to the constant rupturing of the ovarian wall, the ovaries become rough and no longer smooth.
(This is similar to the way that scar-tissue is formed over a bad wound that is re-opened multiple
times.)
-The Ovaries are responsible for secretion of the sex hormone Estrogen

Oocyte Maturation
-Oocyte maturation occurs in the Ovaries
1. A Primary Oocyte (which contains 46 double-structured chromosomes)
undergoes the First Maturation Division which results in a Secondary Oocyte (which contains 23
double-structured chromosomes), and a Polar Body.
2. The Secondary Oocyte (which contains 23 double-structured chromosomes),
undergoes the Second Maturation Division, which results in a Mature Oocyte, and 3 more Polar
Bodies.

Menstruation
-Typically 28 days in length
-Typically begins around ages 11-13
-Contains 3 different phases
1. Menstrual Phase- Bleeding begins (Usually 4-5 days in length)
2. Estrogenic Phase- An increase in FSH (Follicle Stimulating Hormone) during
the first days of the cycle causes a few ovarian follicles to be stimulated. These follicles were produced
via Folliculogenesis. Out of several competing follicles, only one matures to form the Ovum. During
this process the follicles secrete increasing amounts of Estrogen to proliferate the Endometrium.
During this proliferation, the blood vessels and glands grow in size which allows them to create a
thicker lining to result in a cushion for fertilized egg implantation. Once a follicle nears full
maturation, LH (Luteinizing Hormone) is released by the Anterior Pituitary Gland. The release of LH
results in the weakening of the wall of the follicle in the ovary and causes the fully developed follicle to
release its Secondary Oocyte, which matures into an Ovum.
-during most of this phase, estrogen exerts “negative feedback”
(This phase is also known as the Proliferate Phase due to its proliferation of the
endometrium, as well as the Follicular Stage based on its stimulation of the follicles to maturation.)
3. Luteal Phase- After the egg is released from the Ovary, the ruptured follicle
transforms into the Corpus Luteum, which is yellow in appearance. The Corpus Luteum continues to
grow during ovulation and secrete the sex hormone Progesterone, which helps maintain the
Endometrium in its current state since Estrogen production has ceased at this point. Once the egg is
released, it is only able to survive for 24 hours.
-In the case where an egg does not become fertilized, then the
Corpus Luteum will atrophy (die) after 14 days and progesterone secretion will die with it. Falling
levels of progesterone trigger menstruation and the beginning of the next cycle.
-In the case where an egg does become fertilized, the Corpus
Luteum will be preserved by hCG(Human Chorionic Gonadotropin), until the 4th month, in which the
placenta will secrete progesterone and maintain the endometrium in the absence of the Corpus Luteum.
If the Corpus Luteum dies before the 4th month, the result will be a spontaneous abortion. (Many
pregnancy tests use detection of high hCG levels as a determination of pregnancy)

Hormones Involved in Menstruation

1. Gonadotropin-Releasing Hormone (GnRH)- Secreted by the Hypothalamus, and
stimulates the Anterior Pituitary Gland to release FSH and LH
2. Follicle Stimulating Hormone (FSH)- Secreted by the Anterior Pituitary Gland, and
stimulates the follicles to mature, resulting in the secretion of Estrogen by the maturing follicles.
3. Estrogen- Secreted by the maturing follicles in the Ovaries, results in the proliferation of
the Endometrium.
4. Luteinizing Hormone (LH)- Secreted by the Anterior Pituitary Gland, stimulates
ovulation via assisting in rupturing the follicle.
5. Progesterone- First secreted by the Corpus Luteum, maintains the proliferation of the
Endometrium. By the fourth month, the placenta assumes the role of progesterone secretion. If
progesterone levels fall, menstruation is triggered and a new cycle begins.
6. Human Chorionic Gonadotropin (hCG)- secreted by the syncytiotrophoblast of the
developing embryo, this functions to keep the Corpus Luteum alive so that the Corpus Luteum can
continue to secrete progesterone until the placenta can take over at the 4th month.

Fertilization Time frame

1. Fertilized Embryo (Day 1)
2. Two-Cell Stage (Early Day 2)
3. Four-Cell Stage (Late Day 2-Early Day 3)
4. Late Blastocyst (Day 5-6)
`

Gastrulation/ GERMS LAYER FORMATION

 -occurs in the 3rd Week
-begins with the appearance of the Primitive Streak
- three germ layers ALL FROM EPIBLAST
1. Endoderm- Innermost germ layer, forms into the epithelial lining of multiple
systems
2. Mesoderm- Middle germ layer, forms into a number of different tissues and
structures including bone, muscle, connective tissue, and the middle layer of the skin.
3. Ectoderm- Outermost layer of the germ layers in the embryo, it differentiates
to form the nervous system, tooth enamel, and the epidermis.
Organogenesis- formation of the organs.
-Occurs between the 4th and 8th weeks
-Many drugs are pose a threat to the fetus at this developmental stage. Therefore, many
drugs are not given during the first 3 months.
-Morning Sickness is most common during this stage. Previously, the drug “Thalidomide”
was given to prevent morning sickness until it was discovered that the drug was leading to improper
limb development.
-this is notable the most susceptible period for the external factors interfering with the
development and most of the congenital malformations seen at birth find their origin during this critical

Contraindications During Pregnancy

-Alcohol, leads to fetal alcohol syndrome
-Radiation, leads to various genetic defects.

Ultrasonography- most common diagnostic exam to both confirm a birth, as well as scan for any fetal
abnormalities that may complicate the pregnancy.
-Always confirm a pregnancy via ultrasonogram after a positive urine test.
-If anomalies are uncorrectable, it is advisable to recommend medical termination.
-Sex of the child can be identified by the 12th week, depending on the position of the fetus.
-Some underdeveloped countries use ultrasonography as a way to determine the sex so that
they can prevent themselves from having a female child.

Neural Tube Defects

-Neural Tube- the embryo's precursor to the CNS, which contains the Brain and the Spinal
Cord
-Neural Tube Defects can be identified via Amniocentesis, which is a test in which some
amniotic fluid from the amniotic sac, which allows physicians to observe the DNA for any genetic
abnormalities.
-AFP (α-fetoprotein)- if this concentration in the amniotic fluid is abnormally high, then
neural tube defects are likely. This is tested via amniocentesis.
-Folic Acid is given during the first 3 months of the pregnancy to avoid neural tube defects
-Chorionic Villus Biopsy- new technique for measuring genetic defects. The advantage is
that this test can be done from the 8th week also and provides for immediate cell analysis. The
disadvantage is that AFP cannot be analyzed
Ectoderm (Epiblast)
-the outermost germ layer formed during gastrulation
-form the following structures
-CNS -Pituitary
-PNS -Mammary
-Skin -Sweat Glands
-Hair -Sensory Epithelium of Ear Nose and Eye
-Nail

Mesoderm
-the middle germ layer formed during gastrulation
-forms the following structures
-Somites (Muscle Tissue, Cartilage and Bone)
-Vascular System (heart, arteries, veins, lymph vessels, blood cells and lymph
cells)
-Urogenital System (Kidneys, Gonads (Except bladder which is endoderm)
-Spleen
-Suprarenal Glands (also known as Adrenal Glands)
1. Adrenal Cortex- derived from the mesoderm
2. Adrenal Medulla- derived from neural crest cells
-Kidneys are formed by the mesoderm in the sacral region of the body and then
ascend into the lumbar region.

Endoderm (Hypoblast)
-the innermost germ layer formed during gastrulation
-forms the following structures
-GIT -Parathyroid
-Respiratory Tract -Liver
-Urinary Bladder -Pancreas
-Thyroid
-the endoderm also gives rise to the temporary yolk sac

Embryonic Period- the time frame from where fertilization begins until the end of the 2nd month

Fetal Period
-the time period from the beginning of the 3rd month and lasting until the end of intrauterine
life
-During the 5th week the Crown Rump (CR) Length is taken, which is the sitting height of
the fetus. It is measured from the vertex of the skull to the midpoint between the apices of the buttocks.
Also in this time the Crown Heel Length (CHL) can be taken, which is measured from the vertex of the
skull to the vertex of the heels.
-the fetus is covered by a fine hair known as the Lanugo Hair
-movement of the fetus begins in the 2nd month, but the mother will not actually be able to
feel the fetus movements until the 5th month
-the sex of the fetus can be determined in the 12th week
Birth Facts
-at birth the Fetus has 3000gm wt, CR of 36cm, and CH of 50cm
-delivery before the 7th month makes it very difficult for the fetus to survive
-delivery between the 7th and 9th months are able to survive if the external airway and
nutrition are maintained.
-this is mainly because the CNS and respiratory system coordination is not fully
developed in this period
-IUGR is intrauterine growth retardation, and it can be caused by mothers trying to squeeze
their bellies in order to make themselves look skinnier, but in fact it actually compresses the uterine
cavity and prevents the fetus from having the proper space to grow, the resultant is growth retardation
-SGA, small for gestational age, small for dates
-a large fetus is a great risk, post dates and maternal diabetes

Teratology
-this is the study of birth defect and their causes
-the Teratogens are factors causing abnormalities, there are three of them
1. Rubella- heart defects, deafness, cataract, glaucoma
2. Cytomegalovirus- microcephaly, blindness, M.R.
3. X-rays- microcephaly, spina bifida, cleft palate, limb defects
-the following drugs can cause malformation is taken by the mother:
1. Thalidomide- limb defects, heart malformations
2. Aminopterin- anencephaly, hydrocephaly, cleft lip
3. Phenytoin- fetal hydantoin syndrome, M.R.
4. Trimethadione- cleft palate, heart defects, urogenital and skeletal
malformations
5. Lithium- heart malformations
6. Amphetamines- cleft lip and heart defects
7. Warfarin- chondrodysplasia, microcephaly
8. LSD (lysergic acid)- limb and CNS defects
9. Alcohol- fetal alcohol syndrome, heart defects
10. Maternal Diabetes- variety of malformations; heart and neural tube defects
and most commonly noted
11. Ethisterone and Norethisterone- fused labia, musculinization of female
genitalia, clitoral hypertrophy
12. Diethylstilbestrol (DES)- malformations of uterus, uterine tubes, upper
vagina, malformed testes

Fetal Hydantoin Syndrome

- phenytoin abnormalities:
-Craniofacial defects, nail and digital hypoplasia, growth abnormalities, mental
deficiency
Caudal Regression Syndrome
-This is a condition that results in skeletal defects consisting of partial and complete
agenesis of sacral vertebrae in conjunction with hind limb hypoplasia which mainly occurs with
maternal diabetes.

Structural Abnormalities
-in some cases the broken piece of a chromosome is lost and infants with partial deletion of
a chromosome are abnormal
a) Cridu Chat Syndrome- short arm of chromosome 5 (partial deletion of 5th
chromosome)
-features include: microcephaly, micrognatha, M.R., and a high
pitched cat like cry or voice

Structure of a Chromosome
-a chromosome is a very long DNA molecule and associated proteins, that carry portions of
the hereditary information of an organism
-a chromosome is formed from a single DNA molecule that contains many genes
-a chromosomal DNA molecule contains specific nucleotide sequences which are required
for starting replication (replication origin)
-a Centromere attaches to the DNA in the mitotic spindle
-a Telomere is located at each end of the linear chromosome
-the DNA molecule is highly condensed and are packed into units by proteins called
nucleosomes
-there are 23 pairs of chromosomes (22 pairs of autosomes and 1 pair of sex chromosomes)

Mitosis
-the process of a cell division which results in the production of two daughter cells from a
single parent cell
-the two daughter cells are identical to one another and to the original parent cell (same
number of chromosomes)
-there are four phases of mitosis:
1. Prophase- the chromatin diffused (duplicated) during interphase and now
condense in prophase in to the chromosomes, each chromosome has duplicated and now consists of
two sister chromatids. At the end of prophase, the nuclear envelope breaks down into vesicles.
2. Metaphase- the chromosomes align at the equatorial plate and are held in
place by microtubules attached to the mitotic spindle and to part of the centromere.
3. Anaphase- the centromeres divide and sister chromatids separate and move
towards the corresponding poles
4. Telophase- the two daughter chromosomes arrive at each of their poles and
microtubules disappear. The condensed chromatin expands and the nuclear envelope reappears. The
cytoplasm divides, the cell membrane pinches inward which results in the production of two daughter
cells (this is known as cytokinesis)
-the period between cell divisions is known Interphase and is divided into three parts:
1. G1- growth 1 phase (cell size growth as organelles duplicate)
2. S- Synthesis phase (chromosomes are duplicated here)
 3. G2- cell continues to grow and prepare for mitotic division

Prophase I (Meiosis)
-composed of 4 separate steps
1. Leptotene- during this stage, individual chromosomes begin to condense into
long strands within the nucleus; however, the two sister chromatids are still so tightly bound that they
are indistinguishable from one another
2. Zygotene- chromosomes line up with each other into homologous
chromosome pairs.
3. Pachytene- this is the most important stage of prophase I because in this
stage the chromosomes cross over (chiasma) to exchange genetic information, this crossing over is not
able to be seen under a microscope.
4. Diplotene- the chromosomes remain in the chiasmata and the synaptonemal
complex degrades and the homologous chromosomes separate from one another a little bit

Isochromosomes- when the chromosomes are separated horizontally during anaphase instead of being
separated longitudinally

Nondisjunction- the abnormal separation of chromosomes in Meiosis I or sister chromatids in meiosis

II. This is the cause of several medical conditions in human beings

Trisomy 21
-”Down Syndrome”
-there is a high incidence in elderly pregnant primi (first time) mothers (over 30yrs)
-typical features of Down Syndrome include:
a) growth retardation
b) varying degrees of mental retardation
c) all develop signs of Alzheimer's disease after age 35
d) in 95% of cases, the syndrome is cause by meiotic nondisjunction
e) broad flat faces
f) hypotonia
g) simian crease in the hands
h) congenital heart defects (CHD)
i) high incidences of leukemia
j) thyroid dysfunctions

Trisomy 18
-”Edward's Syndrome”
-typical features of Edward's Syndrome include:
a) mental retardation
b) congenital heart defects (CHD)
 c) flexion of fingers
d) low set ears
e) syndactyly
f) micrognathia

Trisomy 13
-”Patau's Syndrome”
-typical features of Patau's Syndrome include:
a) mental retardation
b) congenital heart defects (CHD)
c) cleft lip and palate
d) microphthalmia
e) coloboma- a hole in one structures of the eye such as the iris, retina, etc

Klinefelter's Syndrome
- characterized by XXY
-usually undetected until puberty
-the patient is male in appearance (bb presence Y chromosome)
-typical features of Klinefelter's Syndrome include:
a) Hyalinization of the seminiferous tubules leading to sterility
b) gynaecomastia- development of abnormally large breasts in males
c) the more the number of X's (eg. XXXY), the higher the chance of mental
retardation
d) testicular atrophy

Turner's Syndrome
-Turner's Syndrome characterized by X0 (monosomy)
-98% of all fetuses with the syndrome are spontaneously aborted
-typical features of Turner's Syndrome include:
` a) Gonadal Dysgenesis- absence of ovaries
b) Webbed neck
c) Lymphedema- also known as lymphatic obstruction, is a condition of
localized fluid retention and tissue swelling caused by a compromised lymphatic system
d) Widely spaced nipples

Cridu Chat
-”Cry of the Cat”
-caused specific deletion of a small portion of chromosome 5
-typical features of Cridu Chat are:
a) Severe mental retardation
b) small head with unusual facial features
c) a cry that sounds like a distressed cat

Angelman's Syndrome
 -characterized by inheriting the microdeletion on the long arm of maternal chromosome 15
-typical features of Angelman's Syndrome are:
a) mental retardation
b) cannot speak
c) poor motor development
d) prone to unprovoked and prolonged periods of laughter.

Prader-Willi Syndrome
-characterized inheriting the microdeletion on the long arm of paternal chromosome 15
-typical features of Prader-Willi Syndrome are:
a) mental retardation
b) obesity
c) hypotonia- a state of low muscle tone often resulting in reduced muscle
strength
d) hypogonadism
e) cryptorchidism- the absence of one or both testes from the scrotum

Primordial Germ Cells (PGC)

-these are defined as germ cells (germ cells = cells that give rise to gametes) that have yet
to reach the gonads
-these divide repeatedly on their migratory route through the gut and into the developing
gonads
-PGC are formed in the epiblast (ectoderm) and move to the wall of the yolk sac before
migrating to both sides of the posterior lumbar abdominal wall

Undifferentiated Gonads
-early on in the embryonic development the gonads are indistinguishable as either testes or
ovaries and thus are referred to as undifferentiated gonads
-form in the posterior lumbar region of the abdomen and move downwards
-the undifferentiated gonads are covered by the Coelomic Epithelium which is an epithelial
layer (membrane)
-for sex determination, the Y chromosome contains the testes determining factor (SRY
gene)

Testes
-the testes of the fetus are surrounded by the coelomic epithelium
-consists of many internal sex cords (Medullary Cords) which later develop into the
semniferous tubes
-most of the sex cords are colonized by PGC
-any sex cords not colonized by PGC form the Interstitial Tissue
-cells within the interstitial tissue are known as Leydig Cells, which in response to LH
secretion by the pituitary gland, function to produce testosterone.
-LH also acts to help in the maturation of sperm.
-the point at which all the semniferous tubules come together is known as the Rete Testis
 -within the walls of the semniferous tubules are the Sertoli Cells which have multiple
functions:
1. The tight junctions of the sertoli cells form the blood-testis barrier
2. Sertoli cells also secrete Müllerian Inhibiting Factor (MIF), which functions
to inhibit the development of Müllerian Ducts (which is the predecessor to many of the female
reproductive organs)
-as PGC move down the semniferous tubules they undergo mitosis, then meiosis until near
the end where they acquire a morphological change to acquire the shape of a sperm. The tail end
comes out first and the head comes out of the tubule last. Then the cell moves into the Epididymis to
mature
-PGC mitose into Spermatogonia-A, then into Spermatogonia-B, then into Primary
Spermatocytes (2n4c), meiose into Secondary Spermatocytes (n2c), then 2nd meiosis into a spermatid,
then morphological changes into Sperm.
Spermatocytogenesis -The time period from a Spermatogonia to the completion of
Secondary Spermatocyte
Spermiogenesis.-The time period from the Beginning of a Spermatid to a mature sperm
PGC
↓ (Mitosis)
Spermatogonia-A
↓ (Mitosis)
Spermatogonia-B
↓ (Mitosis)
Primary Spermatocyte
↓ ( 1st Meiosis)
Secondary Spermatocyte
↓ (2nd Meiosis)
Spermatid
↓ (Morphological Change)
Sperm

PGC Maturation
-the period it takes for a PGC to mature into a full sperm takes 64 days
-PGC colonize the semniferous tubules and remain spermatogonia, then upon puberty the
process of forming mature sperm from spermatogonia begins

Teratomas
-these are tumors caused by the misdirection of PGCs, resulting in the PGCs growing into
tumors anywhere in the body.
-these tumors contain tissues derived from all the three germ layers and will express
skeletal cells, muscle cells, epithelial cells, etc
-the most common type of teratoma is the Sacral Coccygeal Teratoma

Oogenesis
-initiated in the 3rd month of the intrauterine life
-if the Testes Determining Factor is not present, then the sex cords of the undifferentiated
gonads will break down into tissue
-the coelomic epithelium descends into the Granulosa Cells (which commonly referred to
as Follicular Cells)
-the Oogonia are formed from the PGC
-during the intrauterine life there are ~7 million Oogonia
-during birth the number of Oogonia decreases to ~2 million
-at the point of puberty the number of Oogonia decreases to ~40,000
-the degeneration of Oogonia over time is known as Atresia
-the initiation of puberty is known as Menarchy
-the average reproductive life in females is ~40 years
-about 480 Ovas are released within one average length reproductive life
-PGC divide by mitosis into oogonia, then again into Primary Oocyte, then undergoes 1st
meiosis and pauses at the end of diplotene phase to remain as a Primary Oocyte until puberty is
initiated, in which it continues onward, this paused phase is referred to as Dictayotene Stage

Oogonia
-Oogonia develop into Ova within the cortex of the ovaries
-within the ovaries there is ovarian tissue, granulosa cells, and oogonia
-one oogonia is typically surrounded by granulosa cells which are then surrounded by a
very thick connective tissue known as the Thicker Internal Ovarian Stroma, which is then surrounded
by a slightly thinner connective tissue layer known as the Thicker External Ovarian Stroma
-the Thicker Internal Ovarian Stroma is rich with blood vessels and secretes the hormone
androgen which diffuses with the granulosa cells where it is converted into Estrogen
-Aromatase is the biochemical enzyme that helps in converting androgen into estrogen.

Follicular Development
-There are four stages of Follicular Development
1. Primordial Follicle
-surrounding each Primary Oocyte are several flattened cells which
eventually form the follicle, and thus are referred to as Follicular
Cells, the Stroma ultimately surrounds these cells
as well
-this complex of Follicular Cells around the Oogonia is referred to
as the Primordial Follicle
-Primordial Follicles secrete the hormone Meiosis Inhibiting
Factor (MIF) which arrests the development of the Primary Oocyte at the end of the Diplotene stage
of Prophase I
-The Follicles remain in this Primordial stage until Menarchy
(initiation puberty)
2. Primary Follicle
-after Menarchy the follicles are stimulated by FSH and promote
the Granulosa cells to become more columnar
-the glycoprotein Zona Pellucida forms between the Oocyte and the
Granulosa cells and provides nutrition to the growing follicle, it
also later induces the “Acrosomal Reaction” during the
fertilization process
-the Granulosa cells proliferate and form the Membrana Granulosa
(hence the name Granulosa Cells)
3. Secondary Follicle
-the beginning of the Secondary Follicle stage is marked by the
development of a cavity within the follicle which rapidly increases in size.
-the cavity is known as the Antrum Folliculi
4. Graafian Follicle
-at this stage the cavity of the follicle expands very rapidly and
pushes the Oocyte to the edge of one cell
-the growing cavity results in many Granulosa cells being squeezed
against the Oocyte and forming a crown like appearance which is known as the Cumulus Oophoricus
-after the follicle ruptures, many granulosa cells from the Cumulus Oophoricus fall out with
the Oocyte and surround the Zona Pellucida in a Sun-Ray type formation known as the Corona Radiata
which functions to provide vital proteins to the cell. The Corona Radiata also prevents any non-
capacitated sperm from entering into contact with the Zona Pellucida. Polyspermia results in
spontaneous abortion.
-After ovulation the remaining granulosa cells within the ruptured follicle acquire a yellow
color and becomes the Corpus Luteum of Menstruation which only has a lifespan of 14 days if there
is no secretion of hCG. If fertilization occurs and the syncytiotrophoblast secretes hCG, then the
Corpus Luteum is now referred to as the Corpus Luteum of Pregnancy which can survive up to the
4th month to continue progesterone secretion, in which the placenta takes over in the progesterone
secretion.
-If no ovulation occurs after fertilization the Corpus Luteum of Pregnancy slowly
becomes white in color and secretes decreased amounts of progesterone until it dies and is referred to
as the Corpus Albicans.

Formation of the Mature Sperm from the Spherical Spermatid

-The Golgi Apparatus forms the Acrosomal Cap
-The Nucleus forms the Head
-The Proximal Centriole situates itself into the Neck
-The Mitochondria form the Muscular Bundle (Sheath) of the Middle Piece
-The Distal Centriole becomes a ring shaped structure at the Bottom of the Middle Piece
that is known as the Annulus
-the Flagellum (tail), grows from the Proximal Centriole within the neck all the way out to
form the tail.
-Capacitation is the event of changes that occur in the sperm upon reaching the uterus.
During this change the glycoprotein layer in the cap is removed on the acrosomal head and it becomes
watery when it was originally thick and hardened in the epididymis. Capacitation actually takes place
in the fallopian tube
-the enzyme Hyaluronidase is released by the acrosome of the sperm after it has reached the
oocyte, in order to digest proteins in the Zona Pellucida and thus enabling conception which is the
Acrosomal Reaction, after this occurs the membrane becomes impermeable to other sperm.

Fertility Issues
-when a couple is unable to conceive the male should undergo a simple semen analysis
before subjecting the female to more difficult testing.
-WHO is the required amount of sperm for fertilization to occur and is 20 million/mL
-a semen analysis will test on motility as well as morphological abnormalities on top of its
testing for sperm count
-exposure to lead (eg. Lead paint or leaded gasoline) decreases sperm count
-Oligospermia is the term for “having too few sperm” which is any amount >20
million/mL
-Aspermia this is the term for having an absence of SEMEN
-Azoospemia this is the term for having an absence of SPERM
-Asthenozoospermia is the term for having weak, sluggish sperm
-females can become infertile from Tubal Occlusion secondary to things like Pelvic
Inflammatory Disease

Infertility Solutions
-there are several different procedures that can be done to assist in fertilization
1. In Vitro Fertilization (IVF)- follicular growth in the ovary is first stimulated
by gonadotropins and then retrieved by laparoscopy. Then the Oocyte is fertilized inside a petri dish
and monitored until the 8-Cell Stage at which time they are placed into the uterus to develop. IVF has
only about a 20-30% success rate. As a result, typically 4-5 Oocytes are collected, fertilized and placed
into the uterus, which can result in multiple births.
2. Zygote Intra-Fallopian Transfer (ZIFT)- fertilized oocytes are placed into
the ampillary region of the fallopian tube. Success rate about 20-30%
3. Gamete Intra-Fallopian Transfer- sperm are physically placed into the
fallopian cavity where an Oocyte is already present due to ovulation. This is most commonly done
due to the male patient having Asthenozoospermia, or weak, sluggish sperm with poor motility.
Only about a 20-30% success rate.
4. Intra-Cytoplasmic Sperm Injection (ICSI)- direct injection of sperm into the
cytoplasm of the Oocyte.

Implantation
-the fertilized egg should take about 2-4 days after fertilization to reach the uterine cavity.
-should occur on about the 6-7th day after fertilization
-blastomere is most commonly implanted into the posterior part of the upper uterine
segment

Semen Contents
1. Sperm
2. Prostate Gland Secretions- Acid Phosphatase and Citric Acid to help negate the acidic
environment of the vagina
3. Seminal Vesicle Secretions- high in Fructose, which give the sperm energy for motility

Four Things that Occur After Fertilization

1. Meiosis II is completed
2. Sex is determined
3. The diploid is established
4. Increased metabolic activity is seen in the zygote

Sperm Pathway
-the sperm move from Testes → Epididymis → Vas Deferens → Ejaculatory Ducts →
Urethra
-sperm must first go through the vagina which has a pH of ~4.3 to 4.5 so it uses the
secretions from the prostate gland to assist in neutralizing the acidity
-then it must pass through the cervix, which normally contains a highly viscous level of
secretions until the luteal phase begins, in which it becomes more watery
-after entering the uterine cavity it takes approximately 2-7hrs to reach the intramural part

Morulla
-after fertilization, cleavage occurs in the zygote leading to different stages of development
-the fertilized cell continues to divide as it moves along the fallopian tube via cilia
movements pushing it, and the contractions produced by the tube. The time it takes for the zygote to
reach the uterine cavity is 2-4 days.
- zygote reaches 16-cell stage = Morulla.
-Morulla is surrounded by the Zona Pellucida to prevent implantation in the Fallopian Tube
until it grows 32 cell stage.
-the cells divide during cleavage to form smaller more compact cells known as blastomeres.
-once the blastomeres reach the third cleavage they begin to maximize their contact with
each other forming a compact ball of cells held together by gap junctions. This process is referred to as
Compaction.

Blastocyst Formation
-Cyst by definition means a fluid filled cavity
-once the morulla reaches the uterine cavity, fluid from uterus enters morulla causing small
cyst to form around the Blastomeres. This cyst, or fluid filled sac, is referred to as the Blastocele.
Now the entire unit is referred to as a Blastocyst.
-the Blastocele pushes the Inner Cell Mass to one side. This Inner Cell Mass will later
form into the embryo, which is why this side of the Blastocyst is referred to as the Embryonic Pole, it is
also commonly referred to as the Embryoblast.
-Conversely to the Inner Cell Mass, there is a single layer of cells pushed to the opposite
side of the Blastocyst which are referred to as the Trophoblast. This structure has a high affinity to
implantation in anything it comes into contact with. The Trophoblast is also known as the
Abembryonic Pole. This layer provides nutrition.

Twins
-sometimes cleavage of the Inner Cell Mass can result in the formation of twins
-There are two main types of twins:
1. Monozygotic Twins- these form as a result of the cleavage of the inner cell
mass into two separate cells
2. Dizygotic Twins- these are formed as a result of the release of more than one
egg from the ovaries. There are two main factors that cause the ovaries to release multiple eggs:
a) Natural release of multiple eggs by the ovaries, typically is more
likely to occur in women over the age of 30.
b) Follicular Stimulation via fertility drugs causing a release of too
many eggs.
-Another type of twin is known as Conjoined Twins which occur when the Inner Cell Mass
doesn't fully separate in a division and thus the two Monozygotic Twins are joined together.

Birth Control
-known as Oral Contraceptive Pills (OCP)
-they are “combined pills” that contain both estrogen and progesterone
 -OCPs function to:
1. Inhibit Follicular Development (which results in no ovulation)
2. Increases the Viscosity of the Mucosal Secretions of the Cervix
3. Inhibition of Implantation
-patient begins OCPs on Day 1 of bleeding
-Placebos are given at the end to withdraw hormones and stimulate bleeding.

Polycystic Ovary Syndrome (PCOS)

-also known as Polycystic Ovarian Disease
-affects 5-10% of women in their reproductive lives (12-45yrs approximately), making it
one of the most common female endocrine disorders and is thought to be one of the leading causes of
female infertility.
-this is a hormonal disorder where you have high levels of androgen and irregular or no
menstrual periods.
-the common features are obesity, anovulation (failure of the ovaries to release an oocyte)
which results in an irregular menses possibly to the point of Amenorrhea (absence of a menstrual
period in women during their reproductive lives), and excessive amounts of androgen.

Implantation
-As the zygote enters the uterine cavity, the Zona Pellucida degenerates by secretions from
the blastomere.
-after degeneration of the Zona Pellucida, the trophoblast, which has a high affinity for
implantation, will implant itself into the posterior wall of the upper uterine cavity.
-the embryo will then dig deep into the endometrium to reach the ends of the maternal
blood vessels so that it can erode them to receive the nutrients from the maternal bloodstream.
-There is NO DIRECT BLOOD FLOW between the mother and fetus.
-the zygote should become completely embedded into the wall of the endometrium to
where it is surrounded on all sides by the endometrium, the embryo doesn't go into the myometrium.
This is known as Interstitial Implantation
-there are three names attributed to Interstitial Implantation:
1. Decidua Basalis- this is the side of the implanted embryo that is most deep
into the endometrium
2. Decidua Capsularis- a capsule structure placed over the implanted embryo on
the external most side covering the abembryonic pole.
3. Decidua Parietalis- the remaining parts of the uterus that is all around the
embryo.
-due to the corrosion of the maternal blood vessels, spotting may occur which can confuse
the patient into thinking there is a failed pregnancy.

Implantation Anomalies
1. Ectopic Pregnancy- this is when the blastocyst implants itself anywhere other than within
the uterine cavity. 95% of ectopic pregnancies occur within the Fallopian Tube, and most of these are
in the ampulla, but ectopic pregnancies can occur anywhere in the abdominal cavity also.
2. Tubal Pregnancy- this is an ectopic pregnancy in which the fertilized egg implants itself
within the fallopian tube. The tube can only sustain the fertilized egg for about one month before it
ruptures and causes severe hemorrhaging in the patient which often leads to shock and death.
3. Abdominal Pregnancy- this is another type of ectopic pregnancy. In this case, the egg
somehow becomes fertilized and falls off the fimbriae of the infundibulum and then implanting itself
into the abdominal cavity, this is also life threatening.

Development of the Embryo

-during the time period of the Interstitial Implantation, the embryo is going through
various changes.
-the inner cell mass forms into a Bilaminar Disk, the Endoderm, and the Ectoderm
-the blastocyst has disappeared by this time
-from the ectoderm some cells will form into the Amniotic Cavity. These ectodermal cells
forming the Amniotic Cavity are also known as Amniogenic Cells.
-from the endoderm, some of the cells form a single layer around the inner aspect of the
trophoblastic layer to form the Primary Yolk Sac. This layer forming the the Primary Yolk Sac is
known as Heusen's Membrane.
-the Trophoblastic layer forms out another layer known as Extra-Embryonic Mesoderm
-within the Extra-Embryonic Mesoderm small vacuoles form independently and come
together to form one large cavity known as the Extra-Embryonic Coelomic Cavity. This cavity is
found in the extra-embryonic mesoderm
-due to the growth of the Extra-Embryonic Coelomic Cavity, the yolk sac is compressed
and decreases in size, consequently becoming the Secondary Yolk Sac.
-as a result of the cavity within the Extra-Embryonic Mesoderm, the EEMD becomes
separated into two different segments.
1. Visceral (splanchnopleuric) Extra-Embryonic Mesoderm- this side is on
the side of the cavity nearer to the yolk sac
2. Somatic (Parietal) Extra-Embryonic Mesoderm- this is on the side of the
cavity that is near the abembryonic pole.
-another new membrane forms between the trophoblast and the extra-embryonic mesoderm
and is known as the Chorionic Membrane.
-also a membrane forms all the way from the top of the amniotic cavity around the
secondary yolk sac and is referred to as the Amniotic Membrane.
Further Development
-the amniotic cavity begins to grow in such a way that it will be able to completely
surround the fetus, so it grows all around the embryo puts a large amount of pressure on EECC, thus
obliterates the Extra-Embryonic Coelomic Cavity.
-once the EECC is obliterated, the EEMD also narrows down and everything comes
together
-the Chorionic and Amniotic Membranes fuse to form the Amniochorionic Membrane.
This is the membrane that feels like a sac of water and ruptures “water-breaking” to signal beginning
birth.
-as the implantation occurs, the trophoblast layer on the decidua basalis side multiplies and
loses its cell membranes which become the Syncytiotrophoblast, this is formed around 14 days from
fertilization, it secretes hCG. There is also a single layer of cells from the trophoblast that does not lose
its membranes, this is known as the Cytotrophoblast.

Villi
-by the beginning of the 3rd week, the trophoblast is characterized by Primary Villi that
consist of a cytrotrophoblastic core (base) covered by a syncytiotrophoblast layer.
-mesodermal cells later penetrate through the core of the primary villi and grow towards the
decidua, the villi now containing mesodermal cells are known as Secondary Villi
-by the end of the 3rd week, mesodermal cells in the core of the Secondary Villi begin to
differentiate into blood cells and small blood vessels, forming a villus capillary system. This villus is
now known as a Tertiary Villi.
-the Chorion also takes part in the development of these villi, consequently they are known
as Chorionic Villi.
-maternal blood falls into the space between the villi which is known as the Inter-Villi
Space, which is where the nutrients from the mother's blood stream are absorbed from, and also where
the fetus's waste is excreted into.
-*the capillaries in the tertiary villi make contact with the capillaries developing in the
mesoderm of the chorionic plate and in the connecting stalk. These blood vessels, in turn, establish
contact with the intra-embryonic circulatory sytem, connecting the placenta and the embryo. Hence,
when the heart begins to beat in the 4th week of development, the villous system is ready to supply the
embryo with essential nutrients and Oxygen.*
-during this time the cytotrophoblastic cells in the villi penetrate progressively into the
overlying syncytium until they reach the maternal endometrium. Here they establish contact with
similar extensions of the neighboring villous stems, forming a thin Outer Cytotrophoblastic Shell.
-the Outer Cytotrophoblastic Shell gradually surrounds the trophoblast entirely and
attaches the chorionic sac firmly to the maternal endometrial tissue to act as a barrier
-the chorionic villi on the Decidua Capsularis side will degenerate eventually and become
smooth in structure, and is then referred to as the Chorionic Levae, and because of this differentiation,
the chorionic villi on the Decidua Basalis side are now referred to as Chorionic Frondosum which
works with the Decidua Basalis to form the placenta
-the Chorionic Frondosum forms the fetal side of the Placenta while the Decidua Basalis
forms the maternal aspect of the placenta.
1. Type 1 Villi (Primary)- contain syncytiotrophoblast and cytotrophoblast
2. Type 2 Villi (Secondary)- contain syncytiotrophoblast, cytotrophoblast, and
Extra-Embryonic Mesoderm
3. Type 3 Villi (Tertiary)- contain syncytiotrophoblast, cytotrophoblast, Extra-
Embryonic Mesoderm, and Fetal Blood Capillaries
'

The Placenta
-the maternal aspect is formed by the Decidua Basalis and the fetal aspect is formed by the
Chorionic Frondosum.
-avg birth diameter is 6 inches and weight is 500g
-umbilical cord attaches to the center ans is formed by the Connecting Stalk
-the surface of the fetal side is smooth due to the chorionic and amniotic membranes, but
the maternal side is rough due to the presence of Cotyledons, or lobes on the maternal aspect.
-these maternal cotyledons are formed by the division of the placenta by septums
 -maternal hormones never cross the placental barrier, but synthetic hormones will cross
the placental barrier (eg. Ethisterone) Some synthetic progestins can cause masculinization of
female fetuses.
-O2 and Carbohydrates (various nutrition products), diffuse from the maternal blood into
the fetal blood stream, and the fetal waste products (urea, CO2 and other nitrogenous waste products)
diffuse from the fetal blood stream into the maternal blood stream for excretion.
-IgG (Immunoglobulin-G) is the only immunoglobulin that is capable of crossing the
placental barrier which acts as a protection against disease for the fetus.
-the placenta has four main hormones that it secretes:
1. Estrogenic Hormones- promotes the development of the mammaries
2. Progesterone- maintains the proliferated state of the endometrium
3. hCG- maintains the Corpus Luteum until the placenta can secrete adequate
amounts of progesterone
4. Somatomammotropin- a growth hormone-like substance that gives the fetus
priority on maternal blood glucose and makes the mother somewhat diabetic. It also promotes the
breast development for milk production. This is often referred to as an “Anti-Insulin” hormone.
-minimum of 30 minutes after birth of the baby, the placenta will remain attached to the
uterine wall. During this time it is constricting its blood vessels (to minimize bleeding) and separating
itself from the uterine wall. If a clinician were to pull on the umbilical cord (which is now cut and
hanging out the vagina) before the placenta were to detach itself then it could cause severe
hemorrhaging and shock which can consequently result in death of the mother.

Threatened Abortion
-a condition that occurs within the first 20 weeks of pregnancy in which an increase in
vaginal bleeding indicates an increased risk in the possibility of a miscarriage.

Gestational Diabetes
-this is a condition in which women without previously diagnosed diabetes that exhibit high
blood glucose levels during pregnancy.
-it is believed that hormones produced during pregnancy can increase a woman's resistance
to insulin, resulting in an impaired glucose tolerance that disappears after birth.
-babies born to gestational diabetics typically have an increased risk of conditions such as:
a) Large for Gestational Age
b) Low Blood Sugar
c) Jaundice

Anomalies of the Placenta

1. Bilobed Placenta (Bidiscoidal Placenta)- a morphological abnormality in which two
portions of a normal placenta are separate in their attachments to the endometrium but connected by
thin segments of placenta or blood vessels. It looks like two placentas branching from the umbilical
cord.
2. Lobed Placenta- many lobes show up with one umbilical cord
3. Diffuse Placenta- when chorionic villi persist all around the blastocyst, this causes the
placenta to be thin, and not to assume the shape of a disc.
4. Placenta Succenturiata- when a small part of the placenta is separated from the rest of it.
5. Fenestrated Placenta- when there is a hole in the disc. (like a donut)
6. Circumvallate Placenta- when a peripheral edge of the placenta is covered by a circular
fold of decidua
Placenta Praevia
-this is an anomaly in which the placenta is attached to somewhere other than the upper
uterine cavity
-there are four degrees of Placenta Praevia
1st Degree Placenta Praevia (Low Lying)- this is when the placenta is partially
implanted into both the upper and lower uterine segments but does not touch the Internal Os.
2nd Degree Placenta Praevia (Marginal)- this is when the lower tip of the
placenta is touching the tip of the Internal Os.
3rd Degree Placenta Praevia (Partial)- the placenta is attached to the lower
segment and partially covers the Internal Os at the tip of the placenta
4th Degree Placenta Praevia (Complete)- the placenta is firmly attached to the
lower segment in a way that completely covers the Internal Os.
-1st and 2nd degrees have the possibility of correcting themselves due to the natural
expansion of the uterus.

Vernix Caseosa
-this is the lanugo hair with sebacious secretions covering the newborn baby.
-this has a white and cheese-like appearance

Anomalies of the Amniotic Cavity

-the fluid within the amniotic cavity averages to be around 1000mL-1500mL
-the condition in which the amniotic cavity has less than 1000mL is referred to as
Oligamnios, or Oligohydramnios, is the condition in which there is less amniotic fluid available for
swallowing by the fetus (which allows for filtration through the kidneys and consequently kidney
development), and causes Renal Agenesis, or failure of the kidneys to develop
-the condition of having more than 1500mL of amniotic fluid is referred to as
Hydramnios, also known as Polyhydramnios, which can cause Tracheoesophageal Fistula, which is
where the trachea and the esophagus do not fully separate. Hydramnios can be caused by diabetes
mellitis in the mother.

Formation of the Notocord

-the notocord is defined as the midline structure that develops in the region lying between
the cranial end of the Primitive Streak and the caudal end of the Prochordal Plate
1. The Cranial End of the Primitive Streak proliferates and thickens to become
the Primitive Node
2. A depression appears in the center of the Primitive Node that is known as the
Blastopore. Then other cells of the Primitive node multiplies and passes between the ectoderm and the
endoderm reaching all the way to the caudal margin of the Prochordal Plate
3. These cells extending from the Primitive Streak to the Prochordal Plate is
known as the Notocordal Plate and this undergoes several stages of rearrangement to finally become
the Notocord.

Formation of the Neural Tube

-the neural tube is the preliminary structure to the Brain and Spinal Cord
-this neural tube is actually formed from the ectodermal folding
1. The Caudal End Prochordal Plate forms into the Neural Plate
2. This Neural Plate grows towards the Primitive Streak and begins to fold, the
Lateral Edges of this Neural Plate are the Neural Folds. The cells on the ends of these folds
differentiate and become what are known as the Neural Crest Cells (some of their derivatives are the
Adrenal Medulla, cells in the teeth, and the Melanocytes)
3. The Neural Folds come together near the middle and form the Neural Tube

Subdivisions of the Intra-Embryonic Mesoderm

-originally the Intra-Embryonic Mesoderm is formed by the proliferation of the cells in the
Primitive Streak which then move between the endoderm and ectoderm to form the intra-embryonic
mesoderm
-the Intra-Embryonic Mesoderm inhabits all the space between the Endoderm and
Ectoderm except the following three regions:
a) Prochordal Plate
b) Cloaca
c) Notocord
-there are three subdivisions of the Intra-Embryonic Mesoderm:
a) Paraxial Mesoderm- this is the thickened mesoderm on each side of the
notocord
b) Intermediate Mesoderm- this is the middle layer of the Intra-Embryonic
Mesoderm
c) Lateral Plate Mesoderm- this is the lateral most thinner layer

Paraxial Mesoderm
-by the 3rd week the Paraxial Mesoderm divides into segments known as Somites
-these somites encircle the notocordal process and form the vertebral bodies and degenerate
the notocordal process in all locations where the somites are present. The spaces between the Somites,
where the notocordal process remains, form the Intervertebral Discs (IVD). The central aspect of the
IVD, the remnants of the Notocordal Process form into the Nucleus Pulposas

Lateral Plate Mesoderm

-while the paraxial mesoderm is undergoing segmentation to form the somites, small
cavities begin to form in the Lateral Plate Mesoderm and coalesce (come together) to form the Intra-
Embryonic Coelomic Cavity. This cavity has the shape of a horseshoe and separates the Intra-
Embryonic Mesoderm into two divisions:
a) Somatopleuric (Parietal) Intra-Embryonic Mesoderm- this is the section on
the outside of the horseshoe that is in contact with the ectoderm
b) Splanchnopleuric (Visceral) Intra-Embryonic Mesoderm- this is the inner
section that is in contact with the endoderm
-this Intra-Embryonic Coelomic Cavity has three sections that form into cavities of the
body:
a) Pericardium- this is formed from the apex
b) Pleural Cavities- these are formed by the two areas lateral to the apex
c) Peritoneal Cavity- this is formed by the final two ends of the horseshoe
joining together
-Some portions of the Lateral Plate Mesoderm also help in the development of the limbs
Intermediate Mesoderm
-this differentiates into urogenital structures as well as the undifferentiated gonads

Compression of the Endoderm

-as the Extra-Embryonic Mesoderm continues to grow it begins to compress the Primary
Yolk Sac, making it into a much more compressed Secondary Yolk Sac
-this Secondary Yolk Sac also compresses the Endoderm and fuses with in the center.
-the Endoderm points out at both ends and are known as the Hindgut, and Foregut
respectively. The middle section that has the invagination of the Secondary Yolk sac is known as the
midgut
-the Allantoic Diverticulum originally forms in the midgut but later moves to the hindgut
and attaches to the formation of the apex of the urinary bladder which is forming in the hindgut. The
diverticulum then forms a cord-like structure known as the Median Umbilical Ligament

Bone Tissues
-there are two types of bone tissue:
1. Spongy Bone
2. Compact Bone
-there are three types of cells that contribute to bone homeostasis:
1. Osteoblasts- form bone
2. Osteoclasts- destroy/shape bone
3. Osteocytes- mature cell bones (structural unit)
-an equilibrium between osteoblasts and osteoclasts maintains bone tissue

Compact Bone
-this consists of densely packed osteons, or haversian systems
 -the osteon consists of a central canal the osteonic (haversian) canal, which is surrounded
by concentric rings (lamellae) of matrix.
-between these rings of matrix, the osteocytes are located in spaces called lacunae and
small channels called canaliculi radiate from the lacunae to the haversian canal to provide passageways
through the hard matrix
-these haversian systems in compact bone are so densely packed together that they look like
one solid mass
-the haversian canals contain blood vessels that are parallel to the long axis of the bone.
These blood vessels interconnect, by the way of perforating canals, or canaliculi, with vessels on the
surface of the bone.

Spongy (cancellous) Bone

-lighter and less dense than compact bone.
-consists of plates, or trabeculae, and bars of bone adjacent to small, irregular cavities that
contain red bone marrow

Appositional Growth- when bones increase in diameter during adulthood due to other factors (muscle
activity, weight, etc)

Exam II Anomalies
1. Fibrous Dysplasia- replacement of bone with fibrous tissue, especially the skull and
facial flat bones.
2. Dyschondroplasia (endochondromatosis)- disorderly and excessive proliferation of
cartilage cells in the epiphyseal plate, or the failure of normally formed cartilage to be replaced by bone
which leads to the formation of irregular masses of cartilage within the metaphysis
3. Osteoporosis- low amounts on calcium in the bones make them easy to fracture (mostly
occurs in women after menopause)
4. Multiple Exostoses (diaphyseal aclasis)- multiple bony protrusions develop on the bones
of a child
5. Osteopetrosis- “marble bone disease,” a reduction in osteoclasts results in abnormally
dense bone formation (abnormally dense bone = osteosclerosis)
6. Osteogenesis Imperfecta- calcification of bone may be defective and may result in
multiple fractures
7. Epiphyseal Suppression-

8. Chondro-Osteo Dystrophy- this is a condition that leads to a normal vertebral column but
abnormally short limbs.
9. Cleido-Cranial Dysostosis- this causes an absence of the clavicle as well as the deformity
of some of the facial and skull bones
10. Spina Bifida Anterior- this is when there is an incomplete closure along the anterior
surface of the vertebral column. This can be cause by hemivertebra
11. Spina Bifida- (split spine), this is a birth defect caused by the incomplete closure of the
vertebrae which results in two spinal processes with an opening to the spinal cord between them.
12. Klippel Feil Syndrome- when any two or more of the cervical vertebra fuse together
13. Diastetometamyleia- this is when a bone protrudes into the spinal canal causing either a
splitting, or displacement of the spinal cord
14. Spondylolisthesis- anterior diplacement of the vertebra in relation to the vertebra below
it. This is caused by the improper articulation of one vertebra to another via the articular facets
 15. Pigeon's Chest- a forward projection of the upper part of the sternum (manubrium)
which makes that part of the chest look like a beak
16. Funnel Chest- the diaphragm isn't fully formed and is shortened in length, this causes it
to pull on the bottom of the ribcage, giving it an inward depression and looking like a funnel
17. Arachnodactyly- thin, elongated fingers that resemble “spider-legs,” this is often seen
from Martin's Syndrome
18. Amelia- absence of limbs
19. Phocomelia- malformation of limbs (occurs in thalidomide babies)
20. Polydactyly- excess of digits
21. Syndactyly- two or more digits are fused together
22. Congenital Talipes Equinovarus (“Clubbed Foot”)- this is a congenital birth defect in
which the feet are medially rotated at the ankles. This is common in Edward's Syndrome (Trisomy 18)
23. Folliculitis- infection of a hair follicle
24. Sebacious Cyst- an overactive sebacious gland causes a clogging of the pore resulting
in a blocking of the hair follicle from exiting, consequently an “ingrown hair” is formed
25. Albinism- absence of pigmentation (melanin)
26. Hypertrichosis- excess of hair
27. Atrichia- the absence of hair
28. Amastia- the absence of mammary(ies)
29. Athelia- the absence of nipple(s)
30. Polythelia- the presence of many nipples, this can occur anywhere along the milk line
(which runs all the way down to the groin from the axilla)
31. Gynecomastia- abnormally large breasts in males
32. Polymastia- the presence of more than two breasts
33. Scaphocephaly- excessive fusion (too much overlapping) of the sagittal sutures of the
skull
34. Acrocephaly- excessive fusion (too much overlapping) of the coronal suture with the
parietal sutures
35. Plagiocephaly- non-linear (uneven) sutures
36. Hemivertebra- this is when a vertebra has two ossification centers in its centrum instead
of one and the two form an only “half complete vertebra” that has one side more ossified than the other
37. Achondroplasia- there is insufficient, or disorderly formation of bone in the region of
the epiphyseal cartilage and thus interferes with the growth of long bones making the patient a dwarf.

Annulus Fibrosis is formed by the sclerotome.

Chapter 9: The Pharyngeal Arches

Cliffnotes:
-Pharyngeal Arches: rod-like thickenings of mesoderm present in the wall of the foregut
-at first 6 arches but 5th arch degenerates then 5 remain
-the ventral ends of the arches of the right and left sides meet in the middle line in the floor
of the pharynx
-the interval between any two arches, the endoderm (lining of the pharynx) is pushed
outwards to form a series of pouches. These are called the Pharyngeal Pouches
-opposite of each P pouch, the surface of the ectoderm dips inwards as an ectodermal cleft
-each pharyngeal arch contains own skeletal (cartilege) element, muscle (supplied by the
arch's nerve) and an arterial arch
-the cartilage of the first arch (Meckel's Cartilage) gives rise to the Incus and the Malleus
(of the middle ear)
-the cartilage of the second arch forms the Stapes, the styloid process, and part of the
hyoid bone
-the cartilage of the third arch forms the greater part of the hyoid bone
-the cartilage of the fourth arch and sixth arches give rise to the cartilages of the larynx
-the external acoustic meatus develops from the first ectodermal cleft
-the first endodermal pouch (and part of the second) gives rise to a diverticulum called the
Tubotympanic Recess. The middle ear and the auditory tube develop from the tubotympanic recess
-the palatine tonsil arises from the second pouch
-the inferior parathyroid gland arises from the third pouch
-the superior parathyroid gland arise from the fourth pouch
-the thyroid gland develops mainly from the thyroglossal duct. This duct is formed as a
median diverticulum arising from the floor of the pharynx (at the foramen caecum)

Pharyngeal Arch Formation

-The neck of the embryo is formed by the elongation of the region between the pericardium
and the stromatodaeum (indented area where the head is folding over the pericardium).
-This is mostly achieved by a “decent” of the heart which allows for the appearance of
several mesodermal thickenings in the wall of the cranial-most part of the foregut which are called
Pharyngeal Arches.

Mandibular Arch (1st Arch)

-the nerve of this arch is the Mandibular Nerve
-this forms Meckel's Cartilage which forms the following:
a) Dorsal End- Incus and Malleus
b) Intermediate Portion- Sphenomandibular Ligament and the Anterior
Ligament of the Malleus
c) Anterior End- Mandibular Process
-the mesenchymal cells in the 1st arch is also responsible for formation of bone of the face
including the maxilla, the mandible, the zygomatic bone, the palatine bone, and part of the temporal
bone. First Arch Syndrome leads to the malformation of these structures.
-the muscles from this arch are the muscles of mastication: Medial & Lateral Pterygoids,
Masseter, Temporalis, Mylohyoid, Anterior Belly of the Digastric, Tensor Tympani, and Tensor Palati

Hyoid Arch (2nd Arch)

-the nerve of this arch is the Facial Nerve
-this forms Hyoid Cartilage which forms the following:
a) Stapes
b) Styloid Process of the Temporal Bone
c) Stylohyoid Ligament
d) Smaller Cornua of the Hyoid Bone
e) Upper ½ of the Hyoid Body
-the muscles from this arch form the muscles of facial movement (hence facial nerve):
occipitofronatlis, platysma, stylohyoid, posterior belly of the digastric, stapedius, auricular muscles.

3rd Pharyngeal Arch

-the nerve of this arch is the Glossopharyngeal Nerve
-the cartilage from this arch forms the following structures:
a) Greater Cornua of the Hyoid Bone
b) Lower ½ of the Hyoid Body
-the muscles formed from this arch are the stylopharyngeus muscles, which extend from the
temporal bone to the pharynx

4th Pharyngeal Arch

-the nerve of this arch is the Superior Laryngeal Nerve
-this fuses with the 6th arch to form the cartilages of the Larynx
-this fuses with the 6th arch to form the muscles of the Larynx and Pharynx

5th Pharyngeal Arch

-this almost immediately degenerates

6th Pharyngeal Arch

-the nerve of this arch is the Recurrent Laryngeal Nerve
-this fuses with the 4th arch to form the cartilages of the Larynx
-this fuses with the 4th arch to form the muscles of the Larynx and Pharynx

Pharyngeal Clefts
-these are the small ectodermal gaps formed between the pharyngeal arches. Only the 1st
and 2nd Clefts significant
-the dorsal aspect of the 1st Pharyngeal Cleft forms the External Auditory Canal (the
External Acoustic Meatus)
-the 2nd Pharyngeal Cleft overgrows and forms the smooth/skin? of the neck, leaves a
gap where tissue obliterated = “brachial or cervical cyst.”
If this gap NOT obliterated then it is referred to as the “brachial sinus”
if it has one opening or two openings = "" fistula.

Pharyngeal Pouches
-these are the enclosed inner aspects between the arches and are of endodermal origin
-there are five pouches altogether

1st Pharyngeal Pouch

a) Ventral Aspect- entirely obliterated by the formation of the tongue
b) Dorsal Aspect- joins with the dorsal aspect of the 2nd pouch to form the Tubotympanic
Recess, which in turn forms the Eustachian Tube (Auditory Tube). This tubotympanic recess also
forms the middle ear cavity (middle ear canal)

2nd Pharyngeal Pouch

a) Ventral Aspect- this forms the Tonsilar Pouch
b) Intermediate Region- forms the Tonsils
c) Dorsal Aspect- same as above (joins with the 1st pharyngeal pouch to form the
Tubotympanic Recess)

3rd Pharyngeal Pouch

a) Ventral Aspect- this forms the Thymus (with help from the 4th pouch)
b) Dorsal Aspect- this forms the Inferior Parathyroid Glands
-as the Thymus moves down its tract into the Thorax, it carries the Inferior Parathyroid
Glands down with it and deposits them on the inferior aspect of the Thyroid Gland.

4th Pharyngeal Pouch

a) Ventral Aspect- assists in the formation of the Thymus
b) Dorsal Aspect- this forms the Superior Parathyroid Glands

5th Pharyngeal Pouch

-mostly considered as a part of the 4th pouch
-debatable function

Development of the Thymus

-the Thymus develops from the endoderm of the 3rd Pharyngeal Pouch.
-originally forms in the neck region but moves down into the thorax along a path, carrying
the Inferior Parathyroid Glands with it until it deposits them on the Thyroid.
-Portions of the Thymus many be seen along any point of this pathway and are referred to
as Accessory Thymus Glands.
-this mainly develops during childhood but undergoes involution (regression/atrophy)
during adulthood
-once this gland is in the thorax it gets invaded by lymphoblasts so that it can serve the
function of T-Lymphocyte Production.
Formation of the Thyroid Gland
-this occurs mostly from the Thyroglossal Duct, which takes origin from the Foramen
Caecum and connects the thyroid to the tongue. This duct later degenerates.
-the Thyroid Gland contains two types of cells:
a) Follicular Cells- these are derived from the lower end of the Thyroglossal
Duct
b) Parafollicular Cells- these are derived from the ventral division of the 4th
pouch
-Anomalies of the thyroid gland development are:
1. Lingual Thyroid- the thyroid may lie under the mucosa of the dorsum of the
tongue and may form a swelling that can result in difficulty swallowing
2. Intra-Lingual Thyroid- the thyroid may be embedded in the muscular
substance of the tongue.
3. Suprahyoid Thyroid- the gland may lie in the midline of the neck, above the
hyoid bone
4. Infrahyoid Thyroid- the gland may lie below the hyoid bone, but above its
normal position.
5. Intrathoracic Thyroid- the entire gland, or part of it may lie in the thorax.
6. Ectopic Thyroid- anytime the thyroid, or part of it, is not it its proper location

Cliffnotes:
-the oral cavity is derived partly from the stomatodaeum (ectoderm) and partly from the
foregut (endoderm). These two are separated by the buccopharyngeal membrane that later disappears.
-teeth are formed in relation to the dental lamina. An enlargement of the lamina is formed,
which is called the enamel organ, for each tooth.
-Ameloblasts (derived from ectoderm) form the enamel. Odontoblasts (derived from
mesoderm) form Dentine. The pulp is formed by mesenchyme that invaginates into the enamel organ.
-Three swellings appear in the floor of the pharynx, in relation to the first pharyngeal arch.
These are the right and left Lingual Swellings, and a median swelling known as the Tuberculum
Impar. Another median swelling is formed in relation to the 3rd and 4th arches known as the
Hypobranchial Eminence.
-the anterior 2/3 of the tongue is formed from the lingual swellings and the tuberculum
impar.
-the posterior 1/3 of the tongue is formed by the cranial part of the hypobranchial
eminence
-the salivary glands develop as outgrowths of the buccal epithelium
-the palatine tonsil develops in relation to the 2nd pharyngeal pouch
-the pharynx is derived from the foregut

Formation of the Oral Cavity

-the mouth is derived partly from endoderm and partly from ectoderm. After disappearance
of the buccopharyngeal membrane, the line of junction between the ectoderm and endoderm is difficult
to define.
-in the region of the floor of the mouth, the mandibular processes take part in the formation
of three structures, these are:
1. The lower lip and lower part of the cheeks
2. The lower jaw
3. The tongue.
-these regions eventually become separated via two sulci:
 1. Linguo-Gingival Sulcus- separates the tongue and the gingiva
2. Labio-Gingival Sulcus- separates the cheeks and the gingiva
-another structure to form is the alveolar process which is the indention below the teeth of
the mandible.

Formation of the Tongue

-the medial most parts of the mandibular process proliferate to form two lingual swellings.
These two lingual swellings are partially separated by a median swelling called the Tuberculum Impar.
-another midline swelling is seen in relation to the medial ends of the 2nd, 2rd, and 4th
arches. This swelling is called the Hypo-Branchial Eminence.
a) Anterior 2/3 of the Tongue are formed by the fusion of the Tuberculum
Impar and the Two Lingual Swellings.
b) Posterior 1/3 of the Tongue is formed by the Hypo-Branchial Eminence.
c) Posterior-Most Part of the Tongue is formed by the 4th arch.
-the most caudal portion of the Hypo-Branchial Eminence forms the Epiglottis.
-each section of the tongue is innervated by the nerve supplying its derivative arch.
-the musculature of the tongue is formed by the Occipital Somites
-the anomalies of the tongue are:
a) Macroglossia- the tongue is abnormally large
b) Microglossia- the tongue is abnormally small
c) Aglossia- the tongue is absent
d) The tongue may be bifid due to non-fusion of the two lingual swellings
e) Ankyloglossia- the tongue may be anchored to the floor of the mouth by an
overdeveloped frenulum. This condition greatly affects the patient's speech.
f) Ankyloglossia Superior- the tongue may be anchored to the palate of the
mouth

Formation of the Teeth

-the teeth are formed in relation to the alveolar process. The epithelium overlying the
convex border of this process becomes thickened and projects into the underlying mesoderm. This
epithelial thickening is called the Dental Lamina.
-at regular intervals along the Dental Lamina, Temporary Tooth Buds form as precursors
to “baby teeth” and next to them form Permanent Teeth Buds which are precursors to “adult teeth”
-Originally there is a downgrowth, from the Dental Lamina into the Mesenchymal Cells of
the Alveolar Process, which is referred to as the Enamel Organ. The downgrowth forms a cup shape in
the alveolar process causing compaction of Mesenchymal Cells within the cup area, this mass is called
the Dental Papilla.
-The cells on the epithelium of the cup differentiate into ameloblasts, which function to
secrete Enamel on the superior side of the Dental Organ.
-on the other side of the basement membrane of the Ameloblasts the compacted
Mesenchymal Cells form into Odontoblasts, which function to secrete Dentine on the inferior side of
the Dental Organ.
-the remaining mesenchymal cells of the papilla form the Pulp of the tooth
-after the enamel is fully formed on a tooth, the ameloblasts degenerate. The
odontoblasts, however, continue secreting Dentine from the pulp throughout the life of the tooth
-the Root of the tooth is established by continued growth into the underlying mesenchyme.
Odontoblasts in this region lay down dentine. As layers of dentine are deposited, the pulp space
becomes progressively narrower and is gradually converted into a canal through which nerves and
blood vessels pass into the tooth.
 -in the region of the root there are no ameloblasts, and the dentine is covered by
mesenchymal cells that differentiate into Cementoblasts. These cells lay down a layer of dense bone
called Cementum. Still further to the outside, the mesenchymal cells form the Peridontal Ligament
which connects the root to the socket in the jaw bone.
-the anomalies of the teeth are as follows:
1. Anodentia- one or more teeth may be absent
2. Gemination- two or more teeth may be fused to each other
3. Maloccusion- the alignment of the upper and lower teeth may be incorrect.

Chapter 15: Cardiovascular System

Cliffnotes:
-the heart develops from splanchnopleuric intraembryonic mesoderm related to that
part which forms the pericardial cavity. This mesoderm is referred to as the Cardiogenic Area.
-two endothelial heart tubes (right and left) appear and fuse to form one tube. This tube
has a venous end and an arterial end.
-A series of dilatations appear on this tube. These are the Bulbus Cordis, the Ventricle,
the Atrium, and the Sinus Venosus.
-further subdivisions are named as follows. The bulbus cordis consists of a proximal 1/3
(which is dilated), a middle 1/3 called the Conus, and a distal 1/3 called the Truncus Arteriosus. The
narrow part connecting the Atrium and the Ventricle is the Atrio-Ventricular Canal. The sinus
venosus has right and left horns
-the right and left atria of the heart are formed by partition of the primitive atrium. This
partition is formed by the Septum Primum and the Septum Secundum. A valvular passage, the
Foramen Ovale, is present between these two septa. It allows flow of blood from the right atrium to
the left atrium.
-the dilated proximal 1/3 of the bulbus cordis, the conus, and the primitive ventricle unite to
form one chamber. This is partitioned to form right and left ventricles. This partition is made up of the
following:
1. The Interventricular Septum, which grows upwards from the floor of the
primitive ventricle.
2. The Bulbar Septum, that divides the conus into two parts
3. The gap left between these two is filled by proliferation of atrio-ventricular
cushions that are formed in the atrio-ventricular canal.
-the truncus arteriosus is continuous with the aortic sac. This sac has a right and a left
horn. Each horn is continuous with the Six Pharyngeal Arch Arteries (this is why they are also called
the “Aortic Arches.” These arteries join the dorsal aorta (right or left). The 1st, 2nd, and 5th arch arteries
disappear. The Caudal parts of the right and left dorsal aortae fuse to form one median vessel.
-The ascending aorta and the pulmonary trunk are formed from the truncus arteriosus.
-the arch of the aorta is formed by the aortic sac, its left horn and the left 4th arch artery.
-the descending aorta is formed partly from the left dorsal aorta and partly from the fused
median vessel.
-the brachiocephalic artery is formed from the right horn of the aortic sac
-the common carotid artery is derived from part of the 3rd arch artery
-the pulmonary artery is derived from the 6th arch artery
-the arteries to the gut are formed from the ventral splanchnic branches of the dorsal aorta
-the renal, suprarenal, and gonadal arteries are formed from lateral splanchnic branches
of the dorsal aorta
-arteries to the body wall and limbs are derived from dorsolateral branches of the aorta
-the Left Subclavian Artery is derived from part of the 7th cervical intersegmental artery
-the Right Subclavian Artery is formed partly from the 7th cervical intersegmental artery
and partly from the Right 4th Arch Artery
-the Portal Vein is formed from right and left vitelline veins and anastomoses between
them
-the Superior Vena Cava is derived from part of the right anterior cardinal vein and from
the right common cardinal vein
-the Inferior Vena Cava receives contributions from several veins (and anastomoses
between them). These are the Right Posterior Cardinal Vein, the Right Subcardinal Vein, the Right
Supracardinal Vein, and the Right Hepatocardiac Channel.

Introduction to the Heart

-the heart is of mesodermal origin
-it is formed from Splanchnopleuric Intra-Embryonic Mesoderm lying immediately
Cranial (superior) to the prochordal plate. This section of mesoderm is the Cardiogenic Area, and is
closely related to the pericardial cavity.
-the heart is at first seen in the form of Right and Left Endothelial Heart Tubes that soon
fuse with one another as a result of Cranial-Caudal Folding. The single tube shows a series of
dilatations:
1. Bulbus Cordis
2. Ventricle
3. Atrium
4. Sinus Venosus
-the ventricle and the atrium are connected by a narrow Atrio-Ventricular Canal, and the
Sinus Venosus has Right and Left Horns.
-The Bulbus Cordis lies at the arterial end of the heart and is divided into two segments,
the proximal part is the Conus and the distal part is the Truncus Arteriosus, which is continuous with
the aortic sac.
-The Aortic Sac is continuous with the Right and Left Pharyngeal Arch Arteries.
-the Sinus Venosus lies at the venous end of the heart, and it has Right and Left Horns.

Formation of the Atria

-the Sinus Venosus and the Primitive Atrial Chamber are at first connected by a wide
opening, but gradually the opening becomes more narrow and shifts to the right.
-a narrow slit has right and left margins that are calls Right and Left Venous Valves which
fuse to form a structure called the Venous Valve (aka: Septum Spurium)
-the AV Canal divides into right and left halves due to the formation of the Septum
Intermedium, which is formed from the fusion of endocardial cushions.

Formation of the Interatrial Septum

-the atrial chamber undergoes divisions into right and left halves by the formation of two
septa (that later fuse together)
-First, a narrow septum begins to arise from the roof of the atrium, this septum is known as
Septum Primum, because it is the first septum to form within the Common Atrium. The Septum
Primum continues downward until it reaches the Septum Intermedium, where it eventually fuses.
-before the fusion of the Septum Primum and the Septum Intermedium, the gap inferior to
the Septum Primum allows for blood to flow from the right atrium into the left atrium (bypassing the
pulmonary vasculature) and this gap is called the Foramen Primum (aka: Osteum Primum).
-as the Septum Primum gets closer to fusion with the Septum Intermedium, the Foramen
Primum becomes more narrow and small gaps begin to appear superiorly in the Septum Primum, this
gap is called the Foramen Secundum, which allows for the passage of blood from the right atrium into
the left atrium on the superior-most aspect of the atrium once the Foramen Primum closes.
-after the formation of the Foramen Secundum, a second septum begins to form from the
roof of the atria but stops at the point of the Foramen Secundum. This septum is called the Septum
Secundum. At this point the Foramen Secundum is referred to as the Foramen Ovale.
-After childbirth the pulmonary vasculature is established and the pressure of blood flowing
into the left atrium from the Pulmonary Veins forces the Septum Primum and the Septum Secundum to
fuse, thereby permanently closing the Foramen Ovale.
-In terms of adult anatomy, the Annulus Ovalis represents the lower free edge of the
Septum Secundum and the Fossa Ovalis represents the Septum Primum.

The Right Atrium

-there are three things that contribute for the formation of the Right Atrium
1. The Right ½ of the Common Atrium
2. The Right Horn of the Sinus Venosus
3. The Right Atrio-Ventricular Canal

The Left Atrium

-there are three things that contribute for the formation of the Left Atrium
1. The Left ½ of the Common Atrium
2. The Absorbed portion of the Pulmonary Veins
3. The Left Atrio-Ventricular Canal