First Week of Development: Ovulation to The results of fertilization are:
Implantation a. Restoration of the diploid number of
 With each ovarian cycle, a number of primary
follicles begin to grow, but usually only one
reaches full maturity, and only one oocyte is
discharged at ovulation.
 At ovulation, the oocyte is in metaphase of
the second meiotic division and is surrounded
by the zona pellucida and some granulosa
cells.
Before spermatozoa can fertilize the oocyte, they
must undergo:
1. Capacitation, during which time a
glycoprotein coat and seminal plasma
proteins are removed from the spermatozoon
head.
2. The acrosome reaction, during which acrosin-
and trypsin-like substances are released to
penetrate the zona pellucida.
During fertilization, the spermatozoon must
penetrate:
1. Corona radiata
2. Zona pellucida
3. Oocyte cell membrane
As soon as the spermatocyte has entered the oocyte,
1. The oocyte finishes its second meiotic division
and forms the female pronucleus
2. The zona pellucida becomes impenetrable to
other spermatozoa
3. The head of the sperm separates from the
tail, swells, and forms the male pronucleus
 After both pronuclei have replicated their
DNA, paternal and maternal chromosomes
intermingle, split longitudinally, and go
through a mitotic division, giving rise to the
two-cell stage.
chromosomes
b. Determination of chromosomal sex
c. Initiation of cleavage
Cleavage
- A series of mitotic divisions that results in an
increase in cells, blastomeres, which become
smaller with each division.
 After three divisions, blastomeres undergo
compaction to become a tightly grouped ball
of cells with inner and outer layers.
 Compacted blastomeres divide to form a 16-
cell morula.
 As the morula enters the uterus on the third
or fourth day after fertilization, a cavity begins
to appear, and the blastocyst forms.
- The inner cell mass: formed at the time of
compaction and will develop into the
embryo proper, is at one pole of the
blastocyst
- The outer cell mass: surrounds the inner
cells and the blastocyst cavity, will form
the trophoblast.
 The uterus at the time of implantation is in
the secretory phase, and the blastocyst
implants in the endometrium along the
anterior or posterior wall.
 If fertilization does not occur, then the
menstrual phase begins, and the spongy and
compact endometrial layers are shed.
 The basal layer remains to regenerate the
other layers during the next cycle.
Second Week of Development: Bilaminar Germ
Disc
 At the beginning of the second week, the
blastocyst is partially embedded in the
endometrial stroma
Trophoblast differentiates into:
(1) Cytotrophoblast
- Inner, actively proliferating layer
(2) Syncytiotrophoblast
- Outer layer that erodes maternal tissues
 Lacunae develop in the syncytiotrophoblast
 Maternal sinusoids are eroded by
syncytiotrophoblast
 Maternal blood enters the lacunar network
 By the end of the second week, a primitive
uteroplacental circulation begins.
 The cytotrophoblast forms cellular columns by
penetrating into and surrounded by the
syncytium, these are the primary villi.
 By the end of the second week, the blastocyst
is completely embedded, and the surface
defect in the mucosa has healed.
The inner cell mass or embryoblast differentiates
into:
(1) Epiblast
- Give rise to amnioblasts that line the
amniotic cavity superior to epiblast layer.
(2) Hypoblast
- Continuous with the exocoelemic
membrane, and together they surround
the primitive yolk sac.
 When vacuoles develop in this tissue, the
extraembryonic coelom or chorionic cavity
forms.
 Extraembryonic mesoderm – lines the
cytotrophoblast
 Extraembryonic somatic mesoderm – amnion
 Extraembryonic splanchnic mesoderm – lining
surrounding the yolk sac
The 2nd week of development is known as the week of
2’s:
1. The trophoblast differentiates into 2 layers:
cytotrophoblast & syncytiotrophoblast
2. The embryoblast forms 2 layers: the epiblast
& hypoblast
3. The extraembryonic mesoderm splits into 2
layers: the somatic and splanchnic layer
4. 2 cavities form: the amniotic & yolk sac
cavities.
 Implantation occurs at the end of the 1st
week.
 Trophoblast cells invade the epithelium and
underlying endometrial stroma with the help
of proteolytic enzymes.
 Implantation may also occurs outside the
uterus, such as in the rectouterine pouch, on
the mesentery, in the uterine tube, or in the
ovary. (Ectopic pregnancies)
Third Week of Development: Trilaminar Germ
Disc
 Most characteristic event occurring during the
3rd week is gastrulation.
Gastrulation
 Begins with the appearance of the primitive
streak, which has its cephalic end, the
primitive node.
 In the region of the node and streak, epiblast
cells move inward (invaginate) to form new
cell layers, endoderm and mesoderm.
 Cells that do not migrate through the streak
but remain in the epiblast form ectoderm.
 Epiblast gives rise to all 3 germ layers:
ectoderm, mesoderm & endoderm.
 Prenotochordal cells invaginating in the
primitive pit move forward until they reach
the prechordal plate. They intercalate in the
endoderm as the notochordal plate.
 Notochord
- Forms when the notochordal plate
detaches from the endoderm
- It forms a midline axis, which will serve as
the basis of the axial skeleton.
 Cells in the hypoblast (endoderm) at the
cephalic margin of the disc form the AVE,
which expresses head-forming genes,
including OTX2, LIM1, and HESX1 and the
secreted factor Cerberus.
 Nodal, a member of the TGF-b family of
genes, is then activated and initiates and
maintains the integrity of the node and
streak.
 In the presence of FGF, BMP4 ventralizes
mesoderm during gastrulation so that it forms
Third to Eight Weeks: The Embryonic Period
intermediate and lateral plate mesoderm.
 Chordin, noggin, and follistatin antagonize
BMP4 activity and dorsalize mesoderm to
form the notochord and somitomeres in the
head region. Formation of these structures in
more caudal regions is regulated by the
Brachyury (T) gene.
 Laterality (left–right asymmetry) is regulated
by a cascade of signaling molecules and
genes.
 FGF8, secreted by cells in the node and streak,
induces Nodal and LEFTY-2 expression on the
left side and these genes upregulate PITX2, a
transcription factor and master gene for left-
sidedness.
 The neurotransmitter serotonin (5HT) also
plays a role as a signal molecule upstream
from FGF8.
 Disruption of 5HT levels or misexpression of
PITX2 results in laterality defects, such as
dextrocardia, situs inversus, and cardiac
abnormalities.
 It is possible to construct a fate map of the
epiblast showing this pattern.
 By the end of the third week, three basic
germ layers, consisting of ectoderm,
mesoderm, and endoderm, are established in
the head region, and the process continues to
produce these germ layers for more caudal
areas of the embryo until the end of the
fourth week.
 In the meantime, the trophoblast progresses
rapidly. Primary villi obtain a mesenchymal
core in which small capillaries arise.
 When these villous capillaries make contact
with capillaries in the chorionic plate and
connecting stalk, the villous system is ready
to supply the embryo with its nutrients and
oxygen.
 The embryonic period, which extends from
the third to the eighth weeks of development,
is the period during which each of the three
germ layers, ectoderm, mesoderm, and
endoderm, gives rise to its own tissues and
organ systems.
 As a result of organ formation, major features
of body form are established.
 The ectodermal germ layer gives rise to the
organs and structures that maintain contact
with the outside world:
- Central nervous system
- Peripheral nervous system
- Sensory epithelium of ear, nose, and eye
 - Skin, including hair and nails
- Pituitary, mammary, and sweat glands
and enamel of the teeth
 Induction of the neural plate is regulated by
inactivation of the growth factor BMP4.
 In the cranial region, inactivation is caused by
noggin, chordin, and follistatin secreted by
the node, notochord, and prechordal
mesoderm.
 Inactivation of BMP4 in the hindbrain and
spinal cord regions is effected by WNT3a and
FGF.
 In the absence of inactivation, BMP4 causes
ectoderm to become epidermis and
mesoderm to ventralize to form intermediate
and lateral plate mesoderm.
Components of the Mesodermal Germ Layer:
1. Paraxial
- forms somitomeres, which give rise to
mesenchyme of the head and organize
into somites in occipital and caudal
segments
- Somites give rise to the myotome (muscle
tissue), sclerotome (cartilage and bone),
and dermatome (dermis of the skin),
which are all supporting tissues of the
body.
- The notochord and floor plate of the
neural tube secrete Sonic hedgehog
(SHH), which induces the sclerotome
2. Intermediate
3. Lateral Plate
Two muscle-forming regions differentiate:
1. One is induced in the dorsomedial region of
the somite by WNT proteins secreted by the
dorsal portion of the neural tube.
2. Other is induced in the ventrolateral region of
the somite by a combination of BMP4 and
FGF, secreted by lateral plate mesoderm, and
by WNT proteins, secreted by the overlying
ectoderm.
 The dorsal midportion of the somite becomes
dermis under the influence of neurotrophin 3,
secreted by the dorsal neural tube.
 Mesoderm gives rise to:
- Vascular system
- Urogenital system
- Spleen
- Cortex of the suprarenal glands
 The endodermal germ layer provides:
- Epithelial lining of the gastrointestinal
tract, respiratory tract, and urinary
bladder.
- Also forms the parenchyma of the thyroid,
parathyroids, liver, and pancreas.
- Epithelial lining of the tympanic cavity and
auditory tube originates in the
endodermal germ layer.
 Homeobox genes
- Controls the craniocaudal patterning of
the embryonic axis
- These genes, conserved from Drosophila,
are arranged in four clusters, HOXA,
HOXB, HOXC, and HOXD, on four
different chromosomes.
 As a result of formation of organ systems and
rapid growth of the central nervous system,
the initial flat embryonic disc begins to
lengthen and to form head and tail regions
(folds) that cause the embryo to curve into
the fetal position.
 The embryo also forms two lateral body wall
folds that grow ventrally and close the ventral
body wall.
 Connection with the yolk sac and placenta is
maintained through the vitelline duct and
umbilical cord, respectively.
 The Gut Tube and the Body Cavities
 At the end of the third week, the neural tube
is elevating and closing dorsally, while the gut
tube is rolling and closing ventrally to create a
“tube on top of a tube.”
Lateral plate mesoderm splits to form:
(1) Visceral (splanchnic) layer– associated with
the gut
(2) Parietal (somatic) layer – together with
overlying ectoderm, forms the lateral body
wall folds
 The space between the visceral and parietal
layers of lateral plate mesoderm is the
primitive body cavity.
 When the lateral body wall folds move
ventrally and fuse in the midline, the body
cavity is closed, except in the region of the
connecting stalk.
 The gut tube maintains an attachment to the
yolk sac as the yolk sac (vitelline) duct.
 The lateral body wall folds also pull the
amnion with them so that the amnion
surrounds the embryo and extends over the
connecting stalk, which becomes the
umbilical cord
 Failure of the ventral body wall to close
results in ventral body wall defects, such as
ectopia cordis, gastroschisis, and exstrophy
of the bladder and cloaca.
Third Month to Birth: The Fetus and Placenta
 Parietal Mesoderm will form the:
- Parietal layer of serous membranes
which lines the outside (walls) of the
peritoneal, pleural, and pericardial
cavities
 Visceral layer will form the:
- Visceral layer of the serous membranes
covering the lungs, heart, and abdominal
organs.
 In the gut, the layers form the peritoneum
and in places suspend the gut from the body
wall as double layers of peritoneum called
mesenteries
 Mesenteries provide a pathway for vessels,
nerves, and lymphatics to the organs.
o the gut tube from the caudal end of
the foregut to the end of the hindgut
is suspended from the dorsal body
wall by dorsal mesentery
o Ventral mesentery, derived from the
septum transversum, exists only in
the region of the terminal part of the
esophagus, the stomach, and the
upper portion of the duodenum
 The diaphragm divides the body cavity into
the thoracic and peritoneal cavities.
 It develops from 4 components:
- Septum transversum (central tendon)
- Pleuroperitoneal membranes
- Dorsal mesentery of the esophagus
- Muscular components from somites at
cervical level 3 to 5
 The phrenic nerve arises from these segments
of the spinal cord (C3, 4 & 5)
 The thoracic cavity is divided in to the
pericardial cavity and two pleural cavities for
the lungs by the pleuropericardial
membranes.
 Fetal period
- Extends from the ninth week of gestation
until birth
- Characterized by rapid growth of the body
and maturation of organ systems
 Growth in length is particularly striking during
the 3rd, 4th, and 5th months (approx. 5cm per
month), whereas increase in weight is most
striking during the last 2 months of gestation
(approx. 700g per month)
 Those babies weighing <2.500g (5lb 8 oz) are
considered low birth weight; those below
 The fetal circulation is at all times separated
1,500g (3lb 5oz) are considered very low
from the maternal circulation by:
birth weight.
1. A syncytial membrane (a chorion
 IUGR – a term applied to babies who do not
derivative)
achieve their genetically determined potential
2. Endothelial cells from fetal capillaries
size and are pathologically small.

 Intervillous lakes of the fully grown placenta

 Striking change – the relative slowdown in the
contain approximately 150 mL of maternal
growth of the head
blood, which is renewed three or four times
per minute. The villous area varies from 4 to
 In the 3rd month – about half the size of
14 m2, facilitating exchange between mother
the CRl
and child.
 By the 5th month – about one third of the
CHL
 At birth – one quarter of the CHL
Main functions of the placenta:

(1) Exchange of gases

 th
During the 5 month, fetal movements are (2) Exchange of nutrients and electrolytes
clearly recognized by the mother, and the (3) Transmission of maternal antibodies (provides
fetus is covered with fine, small hair. fetus with passive immunity)
(4) Production of hormones (progesterone,
estradiol, and estrogen, hCG &
 A fetus born during the 6th or the beginning of somatomammotropin
the 7th month has difficulty surviving, mainly (5) Detoxification of some drugs
because the respiratory and central nervous
system have not differentiated sufficiently.
Amnion
 In general, the length of pregnancy for a full-
- a large sac containing amniotic fluid in
term fetus is considered to be 280 days, or 40
which the fetus is suspended by its
weeks after onset of the last menstruation, or
umbilical cord
more accurately, 266 days or 38 weeks after
- the fluid:
fertilization.
1. absorbs jolts
2. allows for fetal movements
3. prevents adherence of the embryo to
Placenta
surrounding tissues
- Consists of 2 components:
1. Fetal portion – derived from the
chorion frondosum or villous chorion
 The fetus swallows amniotic fluid, which is
2. Maternal portion – derived from the
absorbed through its gut and cleared by the
decidua basalis
placenta. The fetus adds urine to the amniotic
- Hemochorial type
fluid, but this is mostly water.

 The space between the chorionic and decidual

Hydramnios
plates is filled with intervillous lakes of
- Excessive amount of amniotic fluid
maternal blood.
- Associated with anencephaly, and
 Villous trees (fetal tissue) grow into the
esophageal atresia
maternal blood lakes and are bathed in them.
 Oligohydramnios
- Insufficient amount of amniotic fluid
- Related to renal agenesis
Umbilical Cord
- Surrounded by the amnion
- Contains:
(1) 2 umbilical arteries
(2) 1 umbilical vein
(3) Wharton’s jelly (protective cushion
for the vessels)
 Dizygotic or fraternal twins
- Have 2 amnions, 2 chorions, 2 placentas
which sometimes are fused
 Monozygotic twins
- Usually have 2 amnions, 1 chorion, 1
placenta
 Conjoined twins
- The fetuses are not entirely split from
each other
- 1 amnion, 1 chorion, 1 placenta
 Parturition (birth)
- Labor usually begins between 34 and 38
weeks
- Labor consists of 3 stages:
1. Effacement and dilatation of the
cervix
2. Delivery of the fetus
3. Delivery of the placenta and fetal
membranes
Birth Defects
 Cleft Lip and Palate
- Most common congenital malformations
of the head and neck
- These environmental factors can affect
the incidence of these disorders:
a. maternal hormonal disorders
b. use of psychiatric medications
c. vitamin and folic acid deficiency
d. hypoxia
e. cigarette smoking
f. maternal obesity and overweight
 Club foot
- The most common congenital deformity
of lower limbs.
- The aim of the treatment is
- To obtain a plantigrate, painless and
functional foot.
- Ponseti method (a conservative treatment
that has a good correction ranging from
as low as 50% to as high as 90%.
- Surgical treatment is indicated only after
failure of conservative methods (”a la
carte” release)
 Microcephaly
- defined usually as having a head
circumference that is ≥3 SDs below the
mean for the age and sex of the infant.
- Rare defect
- May be present at birth or may occur
postnatally
- Associated with a variety of
environmental or infectious conditions &
chromosomal abnormalities:
a. Maternal exposure (tobacco smoke &
alcohol, radiation during pregnancy)
b. Maternal conditions (diabetes
mellitus, phenylketonuria)
c. Infectious disease (herpes, syphilis,
HIV, rubella, toxoplasmosis &
cytomegalovirus)
d. Genetic Factors