Development of Human Body: 2nd
week and Formation of Germ layers:
3rd Week
Gametogenesis/Fertilisation/Embryo
Development
Week 1: days 1-6
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Fertilization, day 1
Cleavage, day 2-3
Compaction, day 3
Formation of blastocyst, day 4
Ends with implantation, day 6
2. Week (2 layered Embryo disc)
• Implantation (Embedding)
• Bilaminar (two layered) embryonic disc,
• Amniotic cavity,
• Umbilical vesicle,
• Connecting Stalk,
• Chorion sac
Week 2: days 714
implantation
-Bilaminar Embryonic Disc-
• Implantation of the blastocyst is completed by the
end of the second week.
• Cells of embryoblast organize into two layers:
• (1) the hypoblast layer, and
• (2) the epiblast layer. Together, the layers form a flat,
almost circular embryonic disc.
8th day
• The second week of development is known as the week of twos:
• The embryoblast forms two layers, the epiblast (5) and hypoblast (7).
• The trophoblast differentiates into two layers, the cytotrophoblast and
syncytiotrophoblast.
• The extraembryonic
mesoderm splits into two
layers, the
somatopleure (10)
and splanchnopleure (11).
• Two cavities, the amniotic (3)
and yolk sac (1) cavities,
form.
Additionally, during the 2nd week;
• Isolated cavities known as lacunae (9)
appear in the syncytiotrophoblast.
• The communication of the eroded
endometrial capillaries with the
lacunae establishes the primordial
uteroplacental circulation.
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A large fluid-filled cavity, the extraembryonic
coelom or chorionic cavity (4), appears within
the extraembryonic mesoderm.
The connecting stalk (6) occurs.
Primary chrionic vili (8) develop.
• The cytotrophoblast cells are mitotically active and
migrate into the increasing mass of syncytiotrophoblast, where they fuse and lose their cell membranes.
• The syncytiotrophoblast is a rapidly expanding,
multinucleated mass in which no cell boundaries are
discernible.
• The erosive syncytiotrophoblast invades the endometrial
connective tissue, and the blastocyst slowly embeds itself
in the endometrium.
• The endometrial cells undergo apoptosis, which facilitates
the invasion.
• The syncytiotrophoblast produces human chorionic
gonadotropin (hCG) which promotes the maintenance of
the corpus luteum, causing it to secrete progesterone.
• The molecular mechanisms of implantation involve
synchronization between the invading blastocyst and a
receptive endometrium.
• The microvilli of endometrial cells (pinopodes), cell
adhesion molecules, cytokines, prostaglandins, growth
factors, and matrix metalloproteins play a role in making
the endometrium receptive.
• As the conceptus implants, the endometrial connective
tissue cells undergo a transformation, the decidual
reaction.
• The connective tissue cells around the implantation site
accumulate glycogen and lipids and assume a polyhedral
appearance.
Endometrium at the time of implantation
• Swollen stromal cells
because of the
accumulation of glycogen
and lipid are known as
decidual cells.
• The primary function of the
decidual reaction is to
provide nutrition for the
early embryo and an
immunologically privileged
site for the conceptus.
• Levels of hCG may be measured in the blood or urine. Most
commonly, this is done as a pregnancy test.
• Enough hCG is produced at the second week to give a positive
pregnancy test, even though the woman is probably unaware that
she is pregnant.
• As known, EPF (early pregnancy factor) is present in the maternal
serum shortly after fertilization. EPF has been detected as soon as
within six hours of conception. EPF is believed to be the earliest
possible marker of pregnancy.
DAY 8
As the erosive
syncytiotrophoblast
invades the endometrial
connective tissue, the
blastocyst is partially
embedded in the
endometrial stroma.
At the meantime, a small
cavity or cleft appears within the inner cell mass. This
cavity enlarges to become the amniotic cavity.
 A layer of high columnar cells between the amniotic cavity and the
hypoblast, the epiblast layer, occurs.
 The epiblast forms the floor of the amniotic cavity and is continuous
peripherally with the amniotic membrane consisting of amnioblasts.
• Meanwhile, flattened cells
probably originating from the
hypoblast form a thin membrane,
the exocoelomic (Heuser's)
membrane that lines the inner
surface of the cytotrophoblast.
• So, the blastocyst cavity becomes
the exocoelomic cavity or
primitive yolk sac.
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The hypoblast forms the roof of the exocoelomic
cavity.
The embryonic disc now lies between the
amniotic cavity and the primitive yolk sac.
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At the time of implantation, the mucosa of the
uterus is in the secretory phase, during which
time uterine glands and arteries become coiled
and the tissue becomes succulent.
Normally, the human blastocyst implants in the
endometrium along the anterior or posterior wall
of the body of the uterus, where it becomes
embedded between the openings of the glands.
myometrium
endometrium
DAYS 9-10
The blastocyst is more
deeply embedded in the
endometrium, and the
penetration defect in the
surface epithelium is closed
by a fibrin coagulum.
Particularly at the
embryonic pole, vacuoles
appear in the
syncytiotrophoblast.
When these vacuoles fuse,
they form large lacunae,
and this phase of
trophoblast development is
known as the lacunar
stage.
8th day
9th day
• During the 9th to 10th days, a new population of cells appears between
the inner surface of the cytotrophoblast and the outer surface of the
exocoelomic cavity.
• These cells, derived from yolk sac cells, form a fine, loose connective
tissue, the extraembryonic mesoderm, which eventually fills all of the
space between the trophoblast externally and the amnion and
exocoelomic membrane internally.
At 10th day, lacunar
network is particularly
evident at the embryonic
pole; at the abembryonic
pole, the trophoblast still
consists mainly of
cytotrophoblastic cells.
Maternal blood and gland
secretion flows into the
lacunae.
The fluid in the lacunae
passes to the embryonic
disc by diffusion.
10th day
DAYS 11-12
 The trophoblastic lacunae at
the embryonic pole are in
open connection with
maternal sinusoids
(congested and dilated
capillaries) in the
12th day
endometrial stroma. So,
primitive uteroplacental
circulation
starts
.
 By day 12, an almost completely regenerated uterine
epithelium covers the closing plug.
 As the syncytiotrophoblast layer grows and expands
toward the abembryonic pole, new lacunae appear also in
this pole.
Soon, large cavities develop within the extraembryonic mesoderm.
• In the meantime, the hypoblast produces additional
endodermal cells that migrate along the inside of the
exocoelomic membrane.
• These cells proliferate and gradually form a new cavity within
the exocoelomic cavity. This new cavity is known as the
secondary yolk sac or definitive yolk sac.
DAYS 13-14
• Secondary yolk sac is much
smaller than the primitive
yolk sac.
• During its formation, large
portions of the exocoelomic
cavity are pinched off.
• These portions are
represented by exocoelomic
cysts.
• When the large cavities in
the extraembryonic
mesoderm become
confluent, they form a new
space known as the
extraembryonic coelom, or
chorionic cavity.
13th day
14th day
• The chorionic cavity surrounds the primitive yolk sac and
amniotic cavity, except where the embryonic disc is
connected to the trophoblast by the connecting stalk.
• With development of blood vessels, the stalk becomes the
umbilical cord.
• The extraembryonic mesoderm lining the cytotrophoblast
and amnion is called the extraembryonic somatopleuric
mesoderm; the lining covering the yolk sac is known as the
extraembryonic splanchnopleuric mesoderm.
• The extraembryonic mesoderm lining the inside of the
cytotrophoblast is known as the chorionic plate.
Thus, the extraembryonic coelom splits the
extraembryonic mesoderm into two layers:
• Extraembryonic somatic mesoderm, lining the
trophoblast and covering the amnion
• Extraembryonic splanchnic mesoderm, surrounding
the umbilical vesicle (yolk sac)
• The prechordal plate develops as a localized thickening of the hypoblast,
which indicates the future cranial region of the embryo and the future site of
the mouth;
• The prechordal plate is also an important organizer of the head region.
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• By the 13th day of development, the
surface defect in the endometrium has
usually healed.
• Occasionally, however, bleeding occurs
at the
implantation site as a result of
increased blood flow into the lacunar
spaces.
• Because this bleeding occurs near the
28th day of the menstrual cycle, it
may be confused with normal
menstrual bleeding
and, therefore, may cause
inaccuracy in determining
the expected delivery date.
• The trophoblast is characterized by villous structures.
• Cells of the cytotrophoblast proliferate locally and
penetrate into the syncytiotrophoblast, forming cellular
columns surrounded by syncytium.
• Cellular columns with the syncytial covering are known
as primary villi.
Primary chorionic villus
Abnormal implantation
• Abnormal implantation sites sometimes occur even within
the uterus.
• Normally, the human blastocyst implants along the
anterior or posterior wall of the body of the uterus.
• Occasionally, the blastocyst implants close to the internal
os (opening) of the cervix, so that later in development,
the placenta bridges the opening (placenta previa) and
causes severe, even life-threatening bleeding in the
second part of pregnancy and during delivery.
• Occasionally, implantation takes place outside the
uterus, resulting in extrauterine pregnancy, or ectopic
pregnancy.
• Ectopic pregnancies may occur at any place in the
abdominal cavity, ovary, or uterine tube. 95% of ectopic
pregnancies occur in the uterine tube, however, and most
of these are in the ampulla.
• In the abdominal cavity, the blastocyst most frequently
attaches itself to the peritoneal lining of the rectouterine
cavity, or pouch of Douglas.
• Sometimes, the blastocyst develops in the ovary proper,
causing a primary ovarian pregnancy.
In most ectopic pregnancies, the embryo dies about the
second month of gestation, causing severe hemorrhaging
and abdominal pain in the mother.
4.5-week human embryo
ECTOPIC TUBAL PREGNANCY
• Abnormal blastocysts are common.
• It is likely that most abnormal blastocysts would not have
produced any sign of pregnancy because their
trophoblast was so inferior that the corpus luteum could
not have persisted.
• These embryos probably would have been aborted with
the next menstrual flow and, therefore, pregnancy would
not have been detected.
• In some cases, however, the trophoblast develops and
forms placental membranes, although little or no
embryonic tissue is present. Such a condition is known as
a hydatidiform mole.
Moles secrete high levels of hCG and may produce benign or
malignant tumors.
Although cells of complete moles are diploid, their entire
genome is paternal.
Thus, most moles arise from fertilization of an oocyte lacking a
nucleus followed by duplication of the male chromosomes.
The exact number of abnormal zygotes formed is
unknown because they are usually lost within 2 to 3 weeks
of fertilization, before the woman realizes she is pregnant,
and therefore are not detected.
Estimates are that as many as 50% of pregnancies end in
spontaneous abortion and that half of these losses are a
result of chromosomal abnormalities.
These abortions are a natural means of screening
embryos for defects, reducing the incidence of congenital
malformations.
Without this phenomenon, approximately 12% instead of
2% to 3% of infants would have birth defects.
Week 3: Days 14-21
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Two layer germ disc
Primitive streak forms
Gastrulation forms tri-laminar embryo
Neural induction
Left-right asymmetry
0.4mm - 2.0mm
On this stage (3rd week)
• Early development of cardiovascular system
• Further diffentiation of chorionic villi
• Neurolation: Development of the neural tube
Gastrulation
At gastrulation the two layered epiblast is converted
into the three primary embryonic germ layers:
– Ectoderm: outside, surrounds other layers later in
development, generates skin and nervous tissue
– Mesoderm: middle layer, generates most of the muscle,
blood and connective tissues of the body and placenta
– Endoderm: eventually most interior of embryo, generates
the epithelial lining and associated glands of the gut, lung,
and urogenital tracts
Formation of trilaminar germ
Trilaminar germ disc
primitive streak, primitive groove
primitive node, primitive pit
3rd week
3rd week
1. Endoderm: primitive groove →hypoblast → endoderm
2. Mesoderm： primitive groove →between epiblast and hypoblat
→mesoderm
3. Ectoderm：epiblast
→ectoderm
The human embryo at gastrulation
At gastrulation, primitive endoderm is replaced by
definitive or embryonic endoderm then mesoderm
is formed
Cell movements during gastrulation
Mesoderm is patterned in a cranial to caudal gradient
Axial mesoderm: passes
through the node and migrates along
the midline –forms the notochord
Paraxial mesoderm:
passes
just caudal to the node and migrates
slightly laterally –forms cartilage,
skeletal muscle, and dermis
Lateral plate mesoderm:
passes more caudal and migrates
more laterally –forms circulatory
system and body cavity linings.
Extraembryonic mesoderm:
passes most caudal and migrates
most laterally –forms extraembryonic
membranes and associated
connective tissue & blood vessels.
Fate of the “axial” mesoderm
The notochord and pre-chordal plate develops from mesoderm arising from cells that passed
directly through the node and migrated cranially along the midline
The notochord and pre-chordal plate are important signaling centers that pattern the
overlying ectoderm and underlying endoderm.
Major signaling centers at gastrulation:
the node and the anterior visceral endoderm (AVE)
• Primitive node positions primitive streak for gastrulation, induces neural differentiation
• AVE from primitive endoderm secretes factors that position primitive streak in posterior, induce head
formation
The node also sets up the neural plate
THE EMBRYONIC PERIOD
 The period in which each of the three germ layers
will give rise to a number of specific tissues and
organs
Ectodermal germ layers
 Initially the ectodermal germ layer has shape of a
disc, not equal at caudal and cranial points
 Notocord and precordal mesoderm induces
overlying ectoderm to thicken and form the
neuro plate
 Induction of neuroectoderm is the initiation of
neurulation
Neurulation
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Process by which neuro tube is formed
from neuro plate
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Lateral edges of neuro plates are elevated
are elevated to form the neuro fold while the
depression makes the neuro groove
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Neuro folding results in formation of a
neural tube
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Communication with amniotic cavity
through neuropores
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Closure of neuropores marks end of
neurulation
Neural crest cells
 These are cells at the lateral border of the
neuroectoderm
 During fusing of the neuro folds the cells will
undergo the epithelial to mesenchymal
transition
 Migrates from neuroectoderm to underlying
mesoderm
 Neuro crest cells of the trunk region start
migrating in 2 directions following closure of
the neuro tube
• Dorsal and ventral
• Ectoderm germ layer gives raise to organs and
structures that maintain contact with the
outside world
Mesodermal germ layer
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Mesodermal germ layer tissue under
goes proliferation
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Midline form a thickened tissue known
as paraxial mesoderm
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Laterally remain thin and called lateral
plate
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Lateral plate divides into somatic or
parietal mesoderm layer continuous with
amnion
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The layer continuous with the yolk sac is
the splanchnic or visceral mesoderm layer
• Paraxial mesoderm
• Segmental organization known as somitomeres
and form in a cephalocaudal manner
• Somitomeres further organise into somites
• First pair arise from the occipital region at
approximately 20th day of development then they
appear at the rate of 3 pairs per day until week 5
• 42 to 44 pairs are present,
• Age determination
Development of Somites
There are;
• 4 occipital,
• 8 cervical,
• 12 thoracic,
• 5 lumbar,
• 5 sacral,
• and 8 to 10 coccygeal pairs. The
first occipital and the last five to
seven coccygeal somites later
disappear, while the remaining
somites form the axial skeleton.
Development of Somites
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Sclerotome
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Myotome
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Dermatome
Development of Somites
• Cells in the dorsolateral of somites form the muscles of the limb and body wall.
• Cells in the dorsomedial of somites migrate under the dorsal epithelial cells to form
myotomes.
Development of Somites
• Myoblasts of the myotome migrate to emerging extremity buds to form limb muscles.
• Lateral plaque mesoderm forms the connective tissues of the extremities.
Development of Somites
• The cells that make up the myotome progress under the dorsal epithelium.
• Dermatome cells lose their epithelial properties when myotome comes to the
ventral and settles under the ectoderm to form the dermis.
Development of Somites
•
Paraxial mesoderm forms segmented regions on both
sides of the neural tube.
• Somitomers in the head region
• Occipital to caudal somites
• Somites
• Sclerotome (Ventromedial)
Vertebra, costa
•
Dermatomyotome (Dorsolateral)
Myoblast, Dermis
(E) Transverse section of an embryo of
approximately 26 days showing the dermatome,
myotome, and sclerotome regions of a somite
Intermediate mesoderm
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Forms segmental cell clusters, future
nephrotome
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More caudally it forms an unsegmented mass
of tissue, the nephrogenic cord
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Excretory units of the urinary system and
gonads form
Lateral plate mesoderm
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Differentiate into visceral and parietal
mesoderm
Differentiation of Lateral Plate Mesoderm
(Formation of Intraembryonic Coelom)
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Small gaps are formed in the lateral and
cardiogenic mesoderm. These combine to form
intraembryonic coelom.
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Intraembryonic coelom continues with
extraembryonic coelom.
Lateral Plate Mesoderm
 Intraembryonic coelom separates lateral mesoderm
into two leaves:
 Visceral (splanchnic, splanchnopleuric) mesoderm;
is continuous with the extraembryonic splanchnic
mesoderm on the vitellus sac.
 Parietal (somatic, somatopleuric) mesoderm; is
continuous with extraembryonic somatic mesoderm
covering the amniotic sac.
Lateral Plate Mesoderm
• Forms lateral and ventral body wall
(somatopleura) with ectoderm on somatic
mesoderm
• Splanchnic mesoderm forms the
splanchnopleura (primitive intestinal wall) with
embryonic ectoderm.
Lateral Plate Mesoderm
 Mesoderm cells facing the coelom cavity form
mesothelial serous membranes.
 In the 4th week, folding of the embryo longitudinally
and laterally intraembryonic coelom divides into
pericardial, pleural and peritoneal cavity. Serous
membranes cover these cavities.
Differentiation of Mesoderm
Differentiation of Mesoderm
• Cartilage, bone and connective tissues
• Smooth and striated muscles
• Blood and lymph cells,
• Heart, blood and lymphatic vessels
• Kidneys, gonads (ovaries and
testicles) and their discharge ways
• Serous membranes covering body
cavities
• Spleen
• Adrenal gland cortex
Endodermal germ layer
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The gastrointestinal tract is the main organ
system derived from the endodermal germ layer
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the epithelial lining of the respiratory tract
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the Parenchyma of the thyroid,
parathyroids, liver, and pancreas
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the reticular stroma of the tonsils and
thymus
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the epithelial lining of the urinary bladder
and urethra
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the epithelial lining of the tympanic cavity
and auditory tube
Development of Primitive Cardiovascular System
Vasculogenesis; development of
vessels
• In 3rd week;
• Development of vessels in;
• Umbilical vesicle (yolk sac)
• Connecting Stalk
starts at the extraembryonic
mesodem of the chorion.
Development of Primitive Cardiovascular System
• Development of intraembryonic
blood vessels starts two days
later.
Vasculogenesis
• Mesenchyme cells gather and differntiate into angioblasts.
These form blood islands.
Vasculogenesis
• Gaps (lumes) are formed in the middle of blood islands. Angioblasts
surrounding the cavity differentiate to primitive endothelial cells.
Vasculogenesis
• The cells inside differentiate to hematopoietic (blood) cells.
• Vessels having lümen and endothel connect with each other to
form vessel networks.
Angiogenesis
• Is the differentiation of new
blood vessels and spreding to
neighbouring sites with the
budding of existing endothel
layer.
Development Of Primitive Blood Cells And Plasma
• In 3rd week
• Vessels of the umbilical and allantois vesicle
develope from endothelial
cells.
• After 5th week
• Intraembryolal blood production starts. Liver,
observed.
spleen and bone marrow is
Development Of Primitive Heart
• Mesenchyme cells at the
cardiogenic region form a pair of
long endocardial heart tube in the
3rd week.
Development Of Primitive Heart
• At the end of 3rd week, intraembryonal,
connecting stalk, chorionic and umbilical sac
vessels and primitive heart tube unite to form
primitive cardiovascular system.
• At the end of 3rd week (day 21-22) heart
starts to beet and blood circulates.
• Cardiovascular system is the first functional
system of the embryo.