General Embryology.pptx

General Embryology
10/12/2023
By Tesfahun (MSc CM)
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Objectives
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General objective
At the end of this session the students will be able to
describe each period of intrauterine life and
development of all systems
Specific objectives
At the end of this course the students will be able to
 List phases of pre natal period
 Discuss each period of intrauterine life
 Explain development of all body systems

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Introduction
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 Embryology is the study of prenatal development, beginning
with gametogenesis up to the formation of full-term fetus.
 a branch of developmental anatomy that studies the changes that
cells, tissues, organs, and the body as a whole undergo from a
germ cell of each parent to the resulting adult.

Significance of embryology
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 Links the gap between prenatal development and obstetrics,
perinatal medicine, pediatrics, and clinical anatomy.
 Develops knowledge concerning the beginnings of human
life and the changes occurring during prenatal development.
 Is of practical value in helping to understand the causes of
variations in human structure.

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Developmental Periods
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Human development is a continuous process that begins when an
oocyte (ovum) is fertilized by a sperm (spermatozoon).divided into
1. Prenatal/Antenatal development (before birth) a
developmental process that represents an amazing integration
of increasingly complexity that occurs from fertilization to
birth.
2. Postnatal (after birth) periods

Pre-natal development
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Lasts 38 weeks from fertilization to parturition, &
divided into three developmental periods
1. Pre-embryonic period (Germinal Period) (0–2
weeks)
2. An Embryonic period (3rd – 8th weeks)
3. Fetal period (9th week - birth)

1. Pre-embryonic (Germinal) Period
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The first two weeks of development and events of pre-embryonic
period include:
 Fertilization
 Transportation of zygote down the uterine tube
 Repeated mitotic divisions/ cleavage or segmentation
 Implantation
 The formation of bilaminar embryonic disc
 Development of the amnion and chorion

2. An Embryonic period (3rd – 8th weeks):
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 Lasts from the beginning of the 3rd Week (day 15) to
the end of the 8th week (day 56).
 During which the primordia of all major organ-systems
develop from the 3 germ layers, hence most important
period in life.
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3. Fetal period:
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 Lasts from 9th week to birth (38 weeks, or 40 weeks from LNMP)
 Period of organ systems growth and differentiation
 Culminates with parturition and birth of the fetus
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Preconditions for the beginning of early development of
embryo
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Gametogenesis: a process of formation and maturation of the
gametes (sperm and ovum) which involves mitosis, meiosis, and
cytodifferentiation.
 Production of gametes
 Reduction of the number of chromosomes by half.
 Two types of gametogenesis: Spermatogenesis and
Oogenesis

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 Gametes are derived from
primordial germ cells (PGCs)
that are formed in the epiblast
during the second week and that
move to the wall of the yolk sac.
 They are originated from the
wall of the yolk sac at the end of
3rd week of embryonic
development.

Cont..
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 These cells migrate from the yolk sac toward the
developing gonads (primitive sex glands), where
they arrive at the end of 4th week and invading the
genital ridges in 6th week of development.
 Hence, the primordial germ cells have an inductive
influence on development of the gonadal ridge into
ovary or testis.

Primordial germ cells
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Yolk sac
 The first human germ cells (primordial germ cells) appear in the
wall of the yolk sac (3rd week)

The germ cells, through amoeboid movement, move
towards the gonads where they arrive at about 5th week
 Primordial cells later differentiate into mature gametes i.e.
spermatogonia (male) or oogonia (female)
Primordialgermcells
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Y
olksac

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 The sex of the embryo is determined at the time of fertilization.
 At 5 weeks gonads appear initially as a pair of longitudinal ridges,
the genital or gonadal ridges.
 6th week: Primordial cell migrate to the ridge, stimulate
development and differentiation of gonads from the primitive
ridge (into either ovary or testis according to the presence or
absence of Y chromosome in the nuclei of those primordial cells)

During 5th week until 7th week male and female genital systems
are similar (development of primitive germ cells) .
7th week: beginning of differentiation of the gonads
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Spermatogenesis (male gametogenesis)
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 is the sequence of events by which spermatogonia are
transformed into mature sperms.
 Takes place in the male gonads ,approximately 300 million sperm
cells are produced daily.
 At puberty, the testes begin to secrete greatly increased
amounts of testosterone, this activates maturation of the
seminiferous tubules, and spermatogenesis.

Oogenesis
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 is the sequence of events by which oogonia are transformed into
mature oocytes (ova).
 This maturation process begins before birth and is completed after
puberty, during child bearing age.
 Oogenesis continues to menopause, which is permanent
cessation of the menses.
 There are less than two million primary oocytes in the ovaries of a
new born female, ranging from 1.2 to 1.6 million, by adolescence
no more than 40,000 remain
 Of these, not more than 500 become secondary oocytes and are
expelled at ovulation during the reproductive period

Abnormal Gametes
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 The ideal maternal age for reproduction is generally considered to
be from 18 to 35 years.
 The likelihood of chromosomal abnormalities in the embryo
increases after the mother is 35.
 During gametogenesis, homologous chromosomes sometimes fail
to separate.
 As a result of this error of meiotic cell division-nondisjunction
some gametes have 24 chromosomes and others only 22

cont….
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 If a gamete with 24 chromosomes unites with a normal
one with 23 chromosomes during fertilization, a zygote
with 47 chromosomes forms .
 This condition is called trisomy because of the presence
of three representatives of a particular chromosome
instead of the usual two.

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 If a gamete with only 22 chromosomes unites with a
normal one, a zygote with 45 chromosomes forms.
 This condition is known as monosomy because only
one representative of the particular chromosome pair
is present.
 For a description of the clinical conditions associated
with numerical disorders of chromosomes.

Fertilization
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 It is a complex process begins with a contact between sperm
& ovum, ends up with mixture of the maternal and paternal
chromosomes.
 Time: 12 - 24 hours after ovulation

Site: ampulla of uterine tube.
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The Laborious Journey of the Sperm
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 An average ejaculate discharges 40-150 million sperm which
eagerly swim upstream toward the fallopian tubes on their
mission to fertilize an egg.
 Only 1% of sperm deposited in the vagina enter the cervix, where
they may survive for many hours.
 Movement of sperm from the cervix to the uterine tube occurs by
muscular contractions of the uterus and uterine tube and very
little by their own propulsion.

Cont…
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 Fast-swimming sperm can reach the egg in a half an hour, while
other may take days (30 minutes or 6 day).
 After reaching the isthmus, sperm become less motile and cease
their migration.
 At ovulation, sperm again become motile, perhaps because of
chemo attractants produced by cumulus cells surrounding the
egg, and swim to the ampulla, where fertilization usually occurs.
 The sperm can live up to 48-72 hours.

Cont…
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 Only a few hundred will even come close to the egg, due to the
many natural barriers and hurdles that exist in the female
reproductive tract.

Cont….
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 If a sperm cell meets and penetrates an egg, it will
fertilize the egg.
 The process takes about 24 hours.

Important events in Fertilization
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Before:
 Capacitation
 Acrosome reaction: release of enzymes from acrosome induced
by, and needed for sperm penetration of, the zona pellucida
During:
 Penetration of corona radiata, zona pellucida and oocyte cell
membrane.
 Recognition: a zona protein ZP3 is responsible for species-
specific fertilization

After entry:
 Cortical reaction: release of cortical granules by the oocyte.
 Zona reaction: zona becomes impenetrable to other sperms through
enzyme release from cortical granules of oocyte to change
structure and composition of the zona pellicuda.
 Spermatozoa are not able to fertilize the oocyte immediately upon
arrival in the female genital tract but must undergo Capacitation
and the acrosome reaction to acquire this capability.
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Capacitation
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 Is a period of conditioning in the female reproductive tract that
lasts approximately 7 hours.
 Much of it occurs in the uterine tube and involves epithelial
interactions between the sperm and the mucosal surface of the
tube.
 Destabilize acrosomal sperm head membrane .
 During this time, a glycoprotein coat and seminal plasma
proteins are removed from the plasma membrane that overlies
the acrosomal region of the spermatozoa.
 Only capacitated sperm can pass through the corona cells and
undergo the acrosome reaction.

Acrosome reaction
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 Occurs after binding to the zona pellucida
 Is induced by zona proteins.
 This reaction culminates in the release of enzymes needed to
penetrate the zona pellucida, including acrosin- and trypsin-like
substances;
 Acrosin
 Hyaluronidase
 Trypsin
 Colagenase
 B- galactocidase
 Esterases

 During fertilization,
the spermatozoon
must penetrate
The corona radiata,
The zona pellucida,
and
The oocyte cell
membrane.
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Phases of Fertilization
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 Fertilization is a sequence of coordinated events
 Passage of the sperm through the cells of the corona radiata
by the effect of:
a)Hyaluronidase enzyme secreted from the sperms.
b)By movement of its tail.
 Penetration of the zona pellucida by acrosine (a substance
secreted from acrosomal cap).
 Fusion of the plasma membranes of the oocyte and the
sperm.

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 Completion of the second meiotic division of the oocyte
& formation of the female pronucleus.
 Formation of the male pronucleus.
As the pronuclei fuse into a single diploid
aggregation of chromosomes, becomes a zygote

92
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Phases of Fertilization
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The oocyte responds in three ways:
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1.Cortical & zona reactions
 Once a receptor has been activated, a series of
reactions to prevent polyspermy (the entrance of more
than one sperm) will be initiated.
 First, the cell surface will be depolarized.
 Then, cortical granules (lysosomes) released into
the perivitelline space will hydrolyze the other
receptors.
 The oocyte membrane becomes impenetrable to
other spermatozoa

Cont…
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2. Completion of the second meiotic division of oocyte
and formation of female pronucleus.
 Penetration of the oocyte by a sperm activates the
oocyte into completing the second meiotic division
and forming a mature oocyte and a second polar
body.
 Following decondensation of the maternal
chromosomes, the nucleus of the mature oocyte
becomes the female pronucleus.

3.Metabolic activation of oocyte
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 Formation of male pronucleus
 Tail detaches and degenerates
 At this stage, the male and female pronuclei are
indistinguishable.
 The two pronuclei fuse eventually, loose nuclear envelops .
 During growth of male and female pronuclei (both haploid) each
replicates its DNA and then undergo first mitotic division.

Results of fertilization
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 Restoration of the diploid number of chromosomes, half
from the father and half from the mother.
 Results in variation of human species as maternal and
paternal chromosomes intermingle.
 Determination of the sex of the new individual.
 Initiation of cleavage.
 Without fertilization, the oocyte usually degenerates 24 hours
after ovulation.

Cleavage
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 A series of mitotic cell divisions, increasing the numbers of
cells but not size.
 These cells, which become smaller with each cleavage
division, are known as blastomeres.
 Until the eight-cell stage,they form a loosely arranged clump.
 After the third cleavage, however, blastomeres maximize their
contact with each other, forming a compact ball of cells held
together by tight junctions.

 It begins about 30 hours after fertilization.
 Zygote divides into 2, then 4, then 8, then 16 cells.
 Zygote lies within the thick zona pellucida during
cleavage.
 It migrates in the uterine tube during cleavage from
lateral to medial.
 Zona pellucida is translucent under the light
microscope.
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Morula
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 When there are 16-32 blastomeres
the developing human is called
morula.
 The Morula reaches the uterine cavity
at this stage.
 Spherical Morula is formed about 3
days after fertilization.
 It resembles mulberry or blackberry.

Blastocyst
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 About the time the morula enters the uterine cavity, fluid
begins to penetrate through the zona pellucida into the
intercellular spaces of the inner cell mass.
 A cavity appears within the morula dividing its cells into 2
groups:
 Outer cell layer called trophoblast.
 Inner cell layer (mass) attached to one of the poles of the
blastocyst.
 The cavity is called blastocystic cavity or blastocele.

 It is the process by which the Blastocyst penetrates the
superficial (Compact) layer of the endometrium of the
uterus.
 The normal site of implantation is the posterior wall of
the uterus near the fundus.
 It begins about the 6th day after fertilization.
 It is completed by the 11th or 12th day.
Implantation
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 The Morula reaches the uterine cavity by the 4th day
after fertilization, & remains free for one or two days.
 Fluid passes from uterine cavity to the Morula.
 Now the Morula is called Blastocyst, its cavity is
called blastocystic cavity, its cells divided into
Embryoblast & Trophoblast.
 By the 5th day the Zona pellucida degenerates to allow
the blastocyst to increase in size and penetrates the
endometrium 10/12/2023
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Why implantation is needed ?
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 The implantation of the blastocyst provides nutrition
to the growing embryo from the maternal blood
initially by diffusion.
 Later through the development of the placenta.
 Then after the development of placenta and
umbilical cord the embryo comes out in to the
uterine cavity

Requirements for Implantation
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 Zona pellucida disappears in time.
 Normal development and transport of the zygote
 Endometrium in secretory phase.
 Normal endocrine regulation

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 Blastocyst begins implantation by the 6th day.
 Trophoblast cells penetrate the epithelium
of the endometrium.
 Penetration results from endometrial cells undergo
apoptosis (programmed cell death), which facilitates
the invasion of the maternal endometrium during
implantation.
 Syncytiotrophoblast engulf these degenerated
cells for nutrition of the embryo. 10/12/2023
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Cont…
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 By 7th day, Trophoblast differentiated into 2 layers:
 Cytotrophoblast, a mononucleated layer of cells that is
mitotically active and forms new cells that migrate into
the increasing mass of syncytiotrophoblast, where they
fuse and lose their cell membranes.
 Syncytiotrophoblast, a rapidly expanding,
multinucleated mass in which no cell boundaries are
discernible.

It is really amazing !
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 By 8th day the blastocyst is
superficially embedded in
the compact layer of the
endometrium.

Ectopic pregnancy:
 Implantation outside the uterus: the uterine tube, abdominal
cavity, or ovary, cervix.
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Second week of development
 Completion of implantation and continuation of
embryonic development.
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Events occur the second week of development
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 Completion of implantation
 Formation of the amniotic cavity, embryonic disc,
and umbilical vesicle
 Development of the chorionic sac and primary chronic
villi

Day 8;
 At this stage the embryo is partly implant in
the endometrium.
 The implantation process initiates the decidual
reaction or decidualization in the uterine stroma, the
cells of which contribute the maternal component of
the placenta.
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 The trophoblast begins to differentiate: its inner part
becomes a single layer of cells, hence its name the
cytotrophoblast
 The outer layer is more extensive and is the invasive
layer is known as the syncytiotrophoblast.
 It is a syncytium, and at this stage, although it has
invaded the endometrium, it has not invaded
endometrial blood vessels.
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Formation of the amniotic cavity, embryonic disc, and
umbilical vesicle.
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 The inner cell mass of the blastocyst has differentiated into
two layers: the upper epiblast and the lower hypoblast.
 These two layers are in contact and form a bilaminar
embryonic disc.
 Epiblast, the thicker layer, consisting of high
columnar cells related to the amniotic cavity
 Hypoblast, consisting of small cuboidal cells
adjacent to the exocoelomic cavity

 Within the epiblast a cavity develops, the amniotic cavity, which
fills with amniotic fluid.
 Some epiblast cells become specialized as amnioblasts, and they
secrete the amniotic fluid.
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 The exocoelomic membrane is derived from the hypoblast
and lines the cavity that appears beneath the hypoblast
forming the primary yolk sac.
 The fluid contained in this sac is the source of nutrition for
the embryo before the placenta is fully formed and
functional.
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Cont….
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 By 12th day of development the blastocyst is
completely embedded in the endometrial stroma.
 The site of the penetration is closed at first by a fibrin
plug which later replaced by the epithelial lining of
the uterus.
 The blastocyst lies in the endometrium& bulges
gradually in the uterine cavity as the development
advances.

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 By 12 days there has been significant change
particularly in the trophoblast.
 Small clefts appear in the syncytiotrophoblast called
lacunae which communicate with the maternal
endometrial sinusoids, there by deriving nutritional
support for the developing embryo.
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 Now blood of maternal capillaries reaches the lacunae
so primordial uteroplacental circulation is established
by 11th or 12th day.
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 Concurrently, extraembryonic mesoderm is formed between the
exocoelomic membrane and the cytotrophoblast.
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 Small clefts appear within the extraembryonic mesoderm splitting
in to two layer
 These cavity merge to form large extra-embryonic coelom that
almost completely surround the embryo and is known as the
chorionic cavity
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 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
 The extraembryonic somatic mesoderm and the two layers of
trophoblast form the chorion.
 The chorion forms the wall of the chorionic sac, within which
the embryo and its amniotic sac and umbilical vesicle are
suspended by the connecting stalk. 10/12/2023
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 The two cavities continue to enlarge, with the amniotic
cavity above the epiblast and the yolk sac below the
hypoblast, now known as the secondary yolk sac
because of the presence of the chorionic cavity
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 By day 13 the lacunae have enlarged substantially.
 The cytotrophoblast has begun to form primary
chorionic villi, which are finger-like protrusions into
the lacunae.
 The embryo is connected to the cytotropoblast by a
connecting stalk of extra-embryonic mesoderm
 This stalk is the forerunner of the umbilical
cord.
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Look this guys…..
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 By the 2nd week the syncytiotrophoblast produces
the hormone human chorionic gonadotrophin
(HCG) ,which maintains the corpus luteum in the
ovary, which in turn sustains the thickness of the
endometrium.
 The hormone is secreted in the urine and thus its
presence is an early indicator of pregnancy.
 This is the basis upon which pregnancy test kits work.

Formationof germ layers andearly tissue and
organ differentiation: thirdweek
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Gastrulation
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 Gastrulation is the formative process by which the
three germ layers and axial orientation are
established in embryos.
 It is the beginning of morphogenesis (development of
body form) and is the significant event occurring
during the third week
 Gastrulation begins with formation of the primitive
streak on the surface of the epiblast

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Primitive Streak
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 The first sign of Gastrulation is the appearance of
“primitive streak” By (15-16day).
 It is groove-like midline depression in the caudal end
of the bilaminar embryonic disc.
 At the cephalic end of the streak the primitive node
develops as a small nodular enlargement consists of a
slightly elevated area surrounding the small primitive
pit.

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cont…
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 Cells of the epiblast migrate toward the primitive streak.
 Upon arrival in the region of the streak, they become flask-
shaped, detach from the epiblast, and slip beneath it.
 This inward movement is known as invagination
 Once the cells have invaginated, some displace the hypoblast,
creating the embryonic Endoderm, and others come to lie
between the epiblast and newly created endoderm to form
Mesoderm.

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 Cells remaining in the epiblast then form Ectoderm.
 Thus, the epiblast, through the process of
gastrulation, is the source of all of the germ layers,
and cells in these layers will give rise to all of the
tissues and organs in the embryo.

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 Cells remaining in the epiblast form ectoderm
 Some displace the hypoblast to form embryonic
endoderm
 Cells that lie between the epiblast and newly created
endoderm form mesoderm. 10/12/2023
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 The mesoderm germ layer spreads
out in all directions to lie between
the ectoderm and the endoderm,
except in two locations, where the
original two germs layers remain in
contact:
1. the prechordal plate, at the
cephalic end of the disc, a
2. The cloacal plate at caudal
end of the disc.
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Prechordal plate
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 A small circular area of columnar
endodermal cells where the
ectoderm and endoderm are in
contact.
 It is the primordium of the
oropharyngeal membrane, located
at the future site of the oral cavity
and may also have a role as a
signaling center for controlling
development of cranial structures

Cont…
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 The cloacal plate is
replaced by the cloacal
membrane.
 In week 4 this membrane
breaks down to establish
communication between the
gut tube and the amniotic
cavity.

Germ layers
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 Each of the three germ layers (ectoderm, mesoderm, and
endoderm) gives rise to specific tissues and organs.
1. Embryonic ectoderm gives rise to
 The surface ectoderm.
 The neuroectodermcentral & peripheral nervous systems.
2. The embryonic mesoderm gives rise to :
 Axial Skeleton , Straited muscle , dermis, Urogenital system.
Connective tissue & smooth muscle of viscera.

Cont…
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3. The embryonic endoderm is the source of the
epithelial linings of the respiratory passages &
gastrointestinal (GI) tract, including the glands opening
into the GI tract & glandular cells of associated organs
such as the liver and pancreas.

Gastrulation
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Notochord
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 Some mesenchymal
cells from the primitive
node and pit migrate
cranially between the
ectoderm and endoderm
until it reaches the
prechordal plate,
forming a median
cellular cord, the
notochordal process.

 Openings develop in the floor of
the notochordal canal and soon
coalesce, leaving a notochordal
plate.
 This plate infolds to form the
notochord
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Function of notochord
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 It forms the basis of the axial skeleton (bones of
the head and vertebral column).
 It induces the overlying ectoderm to thicken and
form the neural plate; the primordium of the
central nervous system.
1/28/2020 170

Cont…
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 Some mesenchymal cells from the primitive streak migrate
cranially on each side of the notochordal process and around the
prechordal plate.
 Here they meet cranially to form cardiogenic mesoderm in the
cardiogenic area where the heart primordium begins to
develop at the end of the third week.

Neurulation
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 The processes involved in the formation of the
neural plate and neural folds and closure of the
folds to form the neural tube constitute
neurulation.
 These processes are completed by the end of the
fourth week, when closure of the caudal neuropore
occurs.

Neural Plate and Neural Tube
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 As the notochord develops, the
embryonic ectoderm over it
thickens to form an elongated,
slipperlike plate of thickened
epithelial cells, the neural plate.
 Neural plate formation is induced
by the notochord.
 The ectoderm of the neural plate
(neuroectoderm) gives rise to the
CNS — the brain and spinal cord.

 On about the 18th day, the neural
plate invaginates along its central
axis to form a longitudinal median
neural groove, which has neural
folds on each side.
 The neural folds become
particularly bulging at the cranial
end of the embryo and are the first
signs of brain development.
 By the end of the third week, the
neural folds have begun to move
together and fuse, converting the
neural plate into a neural tube, the
primordium of the CNS.
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 The neural tube soon separates from the surface ectoderm and
the free edges of the surface ectoderm fuse so that this layer
becomes continuous over the neural tube and the back of the
embryo.
 Subsequently, the surface ectoderm differentiates into the
epidermis.
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Neural Crest Formation
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 Some neuroectodermal cells lying along the crest of each neural
fold lose their epithelial affinities and attachments to neighboring
cells.
 As the neural tube separates from the surface ectoderm, neural
crest cells migrate dorsolaterally on each side of the neural tube.
 They soon form a flattened irregular mass, the neural crest,.

 The neural crest soon
separates into right and left
parts that migrate to the
dorsolateral aspects of the
neural tube.
 Neural crest cells migrate in
various directions and disperse
within the mesenchyme.
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Development of chorionic villi
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 Shortly after primary chorionic villi appear at the end of the
second week, they begin to branch.

 Early in the third week, mesenchyme grows into these primary
villi, forming a core of mesenchymal tissue.
 The villi at this stage-secondary chorionic villi-cover the entire
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 Some mesenchymal cells in the villi soon differentiate into
capillaries and blood cells.
 They are called tertiary chorionic villi when blood vessels are
visible in them.
 The capillaries in the chorionic villi fuse to form arteriocapillary
networks.
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Development of a villus.
A. Transverse section of a primary villus showing a core of
cytotrophoblastic cells covered by a layer of syncytium.
B. Transverse section of a secondary villus with a core of
mesoderm covered by a single layer of cytotrophoblastic cells,
which in turn is covered by syncytium.
C. Mesoderm of the villus showing a number of capillaries and
venules.
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 By the end of the third week, embryonic blood begins to flow
slowly through the capillaries in the chorionic villi
 Oxygen and nutrients in the maternal blood in the intervillous
space diffuse through the walls of the villi and enter the
embryo's blood.
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 Concurrently, cytotrophoblastic cells of the chorionic villi
proliferate and extend through the syncytiotrophoblast to form a
cytotrophoblastic shell, which gradually surrounds the
chorionic sac and attaches it to the endometrium.
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Function of the villi
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 Villi that attach to the maternal tissues through the
cytotrophoblastic shell (anchoring villi).
 Main exchange of material between the blood of the mother
and the embryo takes place.
222

Fourth to Eighth Weeks
Organogenesis period (4th to 8th weeks)
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 All major external and internal structures are
established during the fourth to eighth weeks.
 By the end of this period, the main organ systems have
begun to develop; however, the function of most of
them is minimal except for the cardiovascular system.
 As the tissues and organs form, the shape of the
embryo changes, and by the eighth week, it has a
definitely human appearance.
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 Because the tissues and organs are differentiating
rapidly during the fourth to eighth weeks, exposure
of embryos to teratogens during this period may
cause major congenital anomalies.
 Teratogens are agents such as drugs and viruses that
produce or increase the incidence of congenital
anomalies.

Folding of Embryo
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 Flat trilaminar disc folds into a somewhat
cylindrical embryo.
 Folding occurs in both median & horizontal planes
 Results from rapid growth of the embryo
 Long axis increases rapidly than the sides
 Occurs simultaneously on both axis.
 Constriction at the junction of embryo & yolk sac.

Folding in Median Plane
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 Occurs in the cranial and caudal ends.
 Causing head and tail folds.
 Moving ventrally as the embryo elongates
cranially and caudally.

Head Fold
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 At the beginning of the 4th week neural folds in the
cranial region thickened to form primordium of the
brain.
 Initially the developing brain projects dorsally
into the amniotic cavity.
 Later grows cranially beyond the
oropharyngeal membrane.
 Overhangs the developing heart

 Septum transversum, primordial heart,
pericardial coelom & oropharyngeal
membrane move onto the ventral
surface.
 Endoderm of the yolk sac is
incorporated into the embryo as a
foregut.
 The foregut lies between the brain
& heart
 Oropharyngeal membrane separates
the foregut from the stomodeum.
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 Septum transversum lies caudal to heart after the
folding and develops into central tendon of
diaphragm.
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Tail Fold
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 Results primarily from
growth of the distal part of
the neural tube.
 This is primordium of the
spinal cord.
 As embryo grows, the
caudal eminence projects
over the cloacal
membrane.
 During folding, part of
endoderm is incorporated
into the embryo as a
hindgut.

 Terminal part of the hindgut
soon dilates to form the
cloaca.
 Cloaca is the primordium of
urinary bladder and
anorectal canal
 Before folding primitive
streak lies cranial to the
cloacal membrane
 After folding it lies caudal
to it
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After Tail Fold
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 The connecting stalk
(primordium of umbilical
cord) is attached to the
ventral surface of the
embryo.
 Allantois (a diverticulum
of yolk sac) is partially
incorporated into the
embryo.

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Allantois
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 The allantois appears on
about day 16 as a small out
pouching from the caudal
wall of the yolk sac that
extends into the connecting
stalk.

Allantois
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 A sausage-like diverticulum from the caudal part of the yolk
sac(endoderm origin)
 During the second month, the extraembryonic part of the
allantois degenerates
 Although the allantois is not functional in human
embryos, it is important for: Blood formation occurs in its
wall during the third to fifth weeks.
 Its blood vessels persist as the umbilical vein and arteries.

The intraembryonic part of the allantois runs from the umbilicus
to the urinary bladder,
Form urachus
The median umbilical ligament.
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Median umbilical ligament
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Folding in Horizontal Plane
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 Folding of the sides of the embryo produces right and
left lateral folds (the primordia of the ventrolateral
wall)
 Lateral folding is produced by the rapidly growing
somites.
 Lateral folding or rolling the edges of the embryonic
disc ventrally toward the median plane and forming
a roughly cylindrical embryo

 As the abdominal walls form, part of endoderm is
incorporated into the embryo as the midgut
 Initially there is a wide connection between midgut
& yolk sac
 After folding the connection is reduced to yolk
stalk(omphaloenteric duct) (vitelline duct)
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 By the fifth week, the yolk sac duct, allantois, and umbilical
vessels are restricted to the region of the umbilical ring
 The distal portion of the allantois remains in the connecting
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Folding of Embryo

Control of embryonic development
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 Several control mechanisms guide differentiation and ensure
synchronized development, such as
 Tissue interactions,
 Regulated migration of cells and cell colonies
 Controlled proliferation
 Programmed cell death.
 Each system of the body has its own developmental pattern.
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25
 At the beginning of the fourth week
 The embryo is almost straight
 Has 4 to 12 somites.
 The neural tube is widely open at the rostral and caudal
neuropores .
Highlights of the fourth to eighth weeks
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 By 24 days
 The first two
pharyngeal arches are
visible.
 The first (mandibular arch)
and the second (hyoid arch)
are distinct.
 The heart produces a large
ventral prominence and
pumps blood.
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 By 26 to 27 days
 Three pairs of pharyngeal arches are visible
 The rostral neuropore is closed
 The forebrain produces a prominent elevation of the head
 Upper limb buds are recognizable
 The otic pits (Primordial of internal ear)
 Ectodermal thickenings (lens placodes)
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Anencephaly
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 Is a congenital anomaly characterized by the total or
partial absence of the cranial vault , the covering skin,
and the brain missing or reduced to small mass

By the end of the fourth week
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 Embryo has C-shaped curve
 Rudiments of many of the organ systems( CVS)
 The fourth pair of pharyngeal arches are visible
 The lower limb buds are visible
 Long tail-like caudal eminence ispresent
 The caudal neuropore is usually closed

Spina bifida
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 Spina bifida is a family of
congenital anomalies
defects in the closure of the
spinal column characterized
by herniation or exposure
of the spinal cord and/or
meninges through an
incompletely closed spine.

Fifth Week
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 Enlargement of the head is caused mainly by the rapid
development of the brain and facial prominences.
 The face soon contacts the heart prominence.
 The rapidly growing second pharyngeal arch overgrows the
third and fourth arches, forming a lateral ectodermal
depression on each side-the cervical sinus.
 Changes in body form are minor during the fifth week
compared with those that occurred during the fourth week, but
growth of the head exceeds that of other regions.
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Cervical sinus
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261
 Upper limbs begin to show regional differentiation as the elbows
and large handplates develop .
 Digital rays, begin to develop in the handplates
 Auricular hillocks-develop largely
 Retinal pigment has formed
 The intestines enter the extraembryonic coelom in the proximal
Sixth Week
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262
 The limbs undergo considerable change
 Notches appear between the digital rays in the handplates
 Communication between the primordial gut and umbilical
vesicle is now reduced to a relatively slender duct, the
omphaloenteric duct.
 Ossification of the bones of the upper limbs has begun.
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Seventh Week
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 The digits of the hand are separated but noticeably webbed.
 Notches are now clearly visible between the digital rays of the feet.
 The caudal eminence is still present but thick.
 The scalp vascular plexus has appeared and forms a characteristic
band around the head.
Eighth week
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By the end of Eighth week
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 All regions of the limbs are apparent, the digits have lengthened
and are completely separated.
 Purposeful limb movements first occur during this week.
 Ossification begins in the femur.
 All evidence of the caudal eminence has disappeared by the end
of the eighth week.
 Both hands and feet approach each other ventrally.

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Cont…
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 The embryo has distinct human characteristics.
 However, the head is still disproportionately large,
constituting almost half of the embryo.
 The neck region is established, and the eyelids are
more obvious.
 The eyelids are closing, and they begin to
unite by epithelial fusion.

1/28/2020
Cont…
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 The intestines are still in the proximal portion of the
umbilical cord.
 The auricles of the external ears begin to assume their
final shape.
 Although there are sex differences in the
appearance of the external genitalia, they are not
distinctive enough to permit accurate sexual
identification.

Day 52
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 Period from the beginning of the ninth week to birth.
Characterized by Maturation of tissues and organs
Rapid growth of the body.
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Fetal period( Ninth week to Birth);

9-12 weeks
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 At the beginning of 9th week
 Head ½ of crown-ramp length of the fetus
 Short legs and small thighs
 The liver is the major site of erythropoiesis.
 At 9 weeks the face is broad, the eyes are widely
separated, the ears are low set, and the eyelids are fused.
 Urine formation begins between the 9th and 12th weeks.

½ of the CRL 1/3 of the CRL ¼ of the CRL
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 The sex can be differentiated by external
genitalia by 12 weeks
 By the 11th week, the intestines have
returned to the abdomen
 By the end of week 12
 limbs reach their relative length in comparison with the
rest of the body.
 Primary ossification centers appear in the skeleton
(cranium (skull) and long bones)
 By the end of 12 weeks the spleen will begin
erythropoiesis.

 A 9 week fetus the arrow shows that still the intestine is found in
the proximal part of the umbilical cord.
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 An 11-week fetus :Note its relatively large head and that the
intestines are no longer in the umbilical cord
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Omphalocele
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13 to 16 Weeks
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 Growth is rapid during this period
 Ossification of the fetal skeleton is active during this
period, and the bones are clearly visible on ultrasound
images by the beginning of the 16th week.
 The lower limbs have lengthened.
 Limb movements are visible during ultrasound
examinations.

13 to 16 Weeks
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 Scalp hair patterning is also determined during this
period.
 By 16 weeks, the eyes face anteriorly rather
than anterolaterally.
 The external ears are close to their definitive position
on the sides of the head.
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17 to 18 Weeks
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 Growth slows down during this period, but the fetus still
increases its CRL by approximately 50 mm.
 Fetal movements-quickening-are commonly felt by the mother.
 The skin is now covered with a greasy, cheese like material- vernix
 The vernix protects the fetal skin from abrasions and
hardening that result from exposure to the amniotic fluid with
urine.

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 Eyebrows and head hair are visible at 20 weeks.
 Brown fat (body fat) forms during this period
and is the site of heat production, particularly in
the newborn infant.

The fetuses are usually completely covered with fine downy hair-
lanugo-that helps to hold the vernix caseosa on the skin
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Cont…
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 By 18 weeks, the uterus is formed and canalization of
the vagina has begun.
 By this time, many primordial ovarian follicles
containing oogonia are visible.
 By 20 weeks, the testes have begun to descend.

21-25 weeks
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 There is a substantial weight gain by 24 week,
types II pneumocytes in the
interalveolar walls of the lung have begun to secrete
surfactant.
 At 21 weeks, rapid eye movements begin and
blink- startle responses have been reported at 22 to
23 weeks.

Fingernails are present by 24 weeks.
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Although a 22- to 25-week fetus born prematurely may survive if
given intensive care it may die because its respiratory system is still
immature.
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26-29 weeks
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 A fetus may survive if born prematurely and given intensive care
because lungs are capable of breathing air.
 Eyes open at the beginning of this period.
 The central nervous system has matured to the stage where it can
direct rhythmic breathing movements and control body
temperature.
 By 28 weeks bone marrow become the major site of erythroposis.

30-34 weeks
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 Pupillary light reflex can be produced
 Upper and lower limbs have a chubby appearance
 Fat in the body is about 8% of the body weight

35-38 weeks
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 At 35 weeks fetus will have a firm grasp & show a spontaneous
orientation to light.
 Secondary ossification centers appear in the epiphyses
 Amount of fat changes to 16% of body weight
 The nervous system is sufficiently mature to carry out some
integrative functions.
 By 36 weeks, the circumferences of the head and abdomen are
approximately equal.

Cont
…
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 After this, the circumference of the abdomen may be greater
than that of the head.
 There is a slowing of growth as the time of birth approach.
 At the time of birth
 Weight of a normal fetus is 3000 to 3400 g
 CRL is about 36 cm
 Sexual characteristics are pronounced, and the testes should be
in the scrotum.

 Preterm:<37 weeks
 Term: 37 to 41 weeks
 Post term:>42 weeks
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The Placenta and Fetal Membranes
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 The chorion, amnion, umbilical vesicle, and allantois
constitute the fetal membranes
 Fetal membranes separate the fetus from the
endometrium and provides protection.

The Placenta
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 The placenta is the primary site of nutrient and gas
exchange between the mother and fetus.
 Nutrients and oxygen pass from the maternal blood
through the placenta to the fetal blood.
 Shortly after birth, the placenta and fetal membranes are
expelled from the uterus as the afterbirth

The Decidua
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 Decidua refers to the gravid endometrium, the
functional layer of the endometrium in a pregnant
woman that separates from the remainder of the
uterus after parturition (childbirth).
 The three regions of the decidua are named according
to their relation to the implantation site:

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 The decidua basalis is the part of the decidua
deep to the conceptus that forms the maternal part
of the placenta.
 The decidua capsularis is the superficial part of
the decidua overlying the conceptus.
 The decidua parietalis is all the remaining parts of
the decidua

Decidua
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Three regions of the
decidua :
 Decidua basalis
Decidua capsularis
Decidua parietalis

Development of the Placenta
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 Early placental development is characterized by the rapid
proliferation of the trophoblast and development of the
chorionic sac and chorionic villi.
 Chorionic villi cover the entire chorionic sac until the
beginning of the eighth week.
 As pregnancy advances, villi on the embryonic pole
continue to grow and expand, giving rise to the chorion
frondosum (bushy chorion)

Chorion
frondosum
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 Villi associated with the
decidua capsularis are
compressed, reducing the blood
supply to them.
 By the 3 rd month (smooth
chorion (chorion laeve)
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 By 22 to 24 weeks, the reduced blood supply to the decidua
capsularis causes it to degenerate and disappear.
 The smooth part of the chorionic sac fuses with the decidua
parietalis, thereby slowly obliterating the uterine cavity.
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 The only portion of the chorion participating in the exchange
process is the chorion frondosum, which, together with the
decidua basalis, makes up the placenta.
 Fusion of the amnion and chorion to form the amniochorionic
membrane obliterates the chorionic cavity.
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 It is the amniochorionic membrane that ruptures during labor (the
expulsion of the fetus and placenta from the uterus).
 Preterm rupture of this membrane is the most common event
leading to premature labor.
330
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Cont
…
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 Growth in the size and thickness of the placenta
continues rapidly until the fetus is approximately 18
weeks old (20 weeks' gestation).
 The fully developed placenta
 Covers 15% to 30% of the decidua and
 Weighs approximately one sixth of the fetus.

332
 The chorionic villi attach firmly to the decidua basalis
through the cytotrophoblastic shell and anchor the chorionic
sac to the decidua basalis.
 Endometrial arteries and veins pass freely through gaps in
the cytotrophoblastic shell and open into the intervillous
space.
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334
 As the chorionic villi invade the decidua basalis, decidual
tissue is eroded to enlarge the intervillous space.
 This erosion produces several wedge-shaped areas of decidua,
placental septa, that project toward the chorionic plate, the
part of the chorionic wall related to the placenta
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335
 The placental septa divide the fetal part of the
placenta into irregular convex areas cotyledons
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336
 Each cotyledon consists of two or more stem villi and their many
branch villi .
 By the end of the fourth month, the decidua basalis is almost
entirely replaced by the cotyledons
 A number of large arteries and veins, the chorionic vessels,
converge toward the umbilical cord
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Full-term placenta
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 Is discoid with
 22 cm in length
 approximately 3 cm thick
 weighs about 500 to 600 g
 Fetal side
 Smooth, shiny and covered by amnion
 Umbilical vessels radiate from the umbilical cord
 They branch on the fetal surface to form chorionic
vessels.
 Maternal side
 15 to 20 slightly bulging areas, the cotyledons, covered
by a thin layer of decidua basalis, are clearly
recognizable.

3
Fetal side
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39
Maternal side

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 N.B. After birth, the placenta is always inspected for
missing cotyledon.
 Cotyledons remaining attached to the uterine wall
after birth may cause severe bleeding.

Circulation of the placenta
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 Placental circulation consists of independent
circulation of blood in two systems:
 Utero-placental circulation
 A mature placenta has a volume of about 500ml of blood
being occupied in the villi system and 150 ml lying in the
intervillous space.
 The blood of the intervillous spaces is refilled about 3 or 4
times per minute.

343
Feto-placental circulation
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Functions of the placenta
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 Exchange of Gases
 Exchange of Nutrients and Electrolytes,amino acids, free
fatty acids, carbohydrates, and vitamins
 Transmission of maternal
immunoglobulin G (IgG)
 Endocrine Synthesis and Secretion
 HCG
 The steroid hormones synthesized by the
placenta are progesterone and estrogens

Placental Abnormalities
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 Abnormal adherence of chorionic villi to the myometrium is
called placenta accreta
 When chorionic villi penetrate the full thickness of the
myometrium to or through the perimetrium (peritoneal
covering) (placenta percreta).
 When the blastocyst implants close to or overlying the internal
os of the uterus (placenta previa).

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Umbilical Cord
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 It is a soft twisting cord measuring (30- 90) cm in
length (average 55) ,(1-2) cm in diameter.
 It is a pathway between the ventral aspect of the
embryo and the placenta (chorion)
 It has a smooth surface because it is covered by the
amnion

Structure of Umbilical Cord
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 Connecting stalk:
 Allantois & Umbilical vessels
Wharton’s jelly (extra
embryonic mesoderm)
 Yolk stalk (Vitello-intestinal
duct):
 A narrow, elongated duct
which connects gut to yolk sac
 It contains Vitelline Vessels
 (Later on , it is obliterated and
the vitelline vessels disappear

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NormalAttachment of Umbilical Cord
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It is attached to a
point near the centre
of the fetal surface of
the placenta.

Anomalies of Umbilical Cord
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 Battledore placenta : is
attached to the margin of the
placenta (it is not dangerous).
 Velamentous insertion of the
cord : is attached to the
amnion away from placenta,
(It is dangerous to the fetus
due to liability of rupture of
its blood vessels during
labor)

Abnormalities in Length
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 Very Long Cord
 It is dangerous , it may
prolapse or coil around the
fetus.
 Prolapsed cord is compressed
during labor causing fetal
hypoxia or anoxia.

Very Short Cord
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It is dangerous because it may cause premature
separation of placenta, or the cord itself may rupture.

Amnion
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 It is athin, transparent & tough fluid-filled,
membranous sac surrounding the embryo.
 At First : It is seen as a small cavity lying
Dorsal to embryonic plate.
 At Stage of Chorionic Vesicle: The amnion becomes
separated from the chorion by Chorionic Cavity
(extra embryonic coelom).

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 After Folding: the amnion expands greatly and is
becomes on the ventral surface of the embryo.
 As a result of expansion of the amnion, the extra
embryonic coelom is gradually obliterated and
amnion forms the epithelial covering of umbilical
cord.

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Amniotic Fluid
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 It is a watery fluid inside the amniotic cavity (sac).
 It has a major role in fetal growth & development
 It increases slowly, to become (700-1000) ml by full term (37)
weeks.
 Composition
 99% of amniotic fluid is water
 It contains un-dissolved material of desquamated fetal
epithelial cells + organic & inorganic salts
 As pregnancy advances, composition of amniotic fluid
changes as fetal excreta (meconium = fetal feces/& urine) are
added

Sources of amniotic fluid
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 Maternal source:
 Diffusion across amnio-chorionic membrane at the
decidua parietalis.
 Diffusion across chorionic plate from the maternal blood
in the intervillous spaces of the placenta.
 Later, it is derived from
 Fetal source
 Skin,
 Fetal Respiratory tract & Mostly by Excreting
Urine (at beginning of 11th week)

Circulation & Fate of amniotic fluid
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 Amniotic fluid remains constant & in balance
 Most of fluid is swallowed by fetus, and absorbed into fetal
respiratory and digestive tracts, where it is metabolised
 Part of fluid passes through placental membrane into
maternal blood capillaries in intervillus space,
 Other part of fluid is excreted by fetal kidneys and
returned to the amniotic sac through the fetal urinary tract.

Functions of amniotic fluid
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 Provides symmetrical external growth of the embryo
 Acts as a barrier to infection (it is an aseptic medium)
 Permits normal fetal lung development
 Prevents adherence of embryo to amnion
 Protects embryo against external injuries
 Keeps the fetal body temperature constant
 Allows the embryo to move freely, aiding muscular
development in the limbs
 Maintain homeostasis of fluids & electrolytes
 Permits studies on fetal enzymes, hormones and diagnosis of
fetal sex and chromosomal abnormalities

Anomalies of Volume ofAmniotic Fluid
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Oligohydramnios
 A decreased amount of amniotic fluid (less than 400 ml)
 Causes :
 Placental insufficiency with low placental blood flow
 Preterm rupture of amnio-chorionic membrane occurs in
10% of pregnancies
 Renal Agenesis (failure of kidney development)
 Obstructive Uropathy (urinary tract obstruction) lead to
absence of fetal urine (the main source)
Complications :
 Fetal abnormalities (pulmonary hypoplasia,facial &
limb defects)

Polyhydramnios (Hydramnios)
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 An excess amount of amniotic fluid (1500–2000 ml).
 Causes
 Fetal ( 1-20% ) : Esophageal atresia.
 Maternal (2-20%) : Defects in maternal
circulation.
 Idiopathic (3-60%)
 It may be associated with severe anomalies of the CNS

371
Amniotic band syndrome
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 This is a set of congenital malformations attributed to amniotic
bands.
 Occasionally, tears in the amnion result in amniotic bands that
may encircle part of the fetus, particularly the limbs and digits.
 Bands then form from the amnion, like scar tissue, constricting
fetal structures
 Amputations,ring constrictions,and other abnormalities, including
craniofacial deformations, may result.

372
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1/28/2020
Yolk sac development
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 It is large at 32 days.
 It atrophies as pregnancy advances and detaches
itself from the midgut by the end of the 6th week.
 By 10 weeks age it has shrunk to a pear-shaped
remnant about 5 mm in diameter and remains
connected with the midgut by a narrow yolk stalk.
 By 20 weeks age is invisible.

Dr. L. Tchakarov
37
3 weeks 4 weeks
20 weeks 10 weeks 10/12/2023
220

Fetal Circulation
The main features of the fetal circulation are:
 Nonfunctioning lungs
 Course of the blood from the placenta to the heart
 Three shunts permitting the blood to bypass the liver
and lungs:
 Foramen ovale
 Ductus venosus
 Ductus arteriosus
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 The oxygenated blood from the
placenta reaches the fetus by
umbilical vein
 Most of the blood bypasses the
liver through the ductus venosus,
although little blood enters the
liver
 In the inferior vena cava, the
oxygenated blood mixes with the
deoxygenated blood arriving from
the fetus

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 IVC opens into the right atrium. In the right atrium,
the caval blood is guided into the left atrium
through the foramen ovale.
 However, little blood remains in the right atrium,
which mixes with the blood arriving through the
superior vena cava.
 In the left atrium also, the oxygenated blood mixes
with deoxygenated blood arriving from the lungs.

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 Blood enters the left ventricle and then into the
ascending aorta. Thus the heart and the brain receive
better oxygenated blood.
 The blood from the right atrium enters into the right
ventricle, and from there into the pulmonary artery.
 Most of the blood from the pulmonary artery enters
into the aorta through the ductus arteriosus.
 From the aorta, the blood is distributed to body
tissues and flows through the umbilical arteries into
the placenta.

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 The blood circulating in the
fetal arterial system is not
fully oxygenated
 There is mixing of
oxygenated and
deoxygenated blood in the:
I. Liver sinusoids
II. Inferior vena cava
III. Right atrium
IV. Left atrium
V. Descending aorta.
I
II
V
IV
III

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What happens at birth?
Oh… let me take a
deep breath… and
then everything will
be OK

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 At birth, dramatic changes occur in the circulatory
pattern.
 The changes are initiated by baby’s first breath.
 Fetal lungs begin to function
 Placental circulation ceases
 The three shunts that short-circuited the blood
during the fetal life cease to function

1. The infant’s lungs begin to function:
 The lungs inflate, which tends to draw blood from
the right ventricle.
 Oxygenated blood from the lungs passes through
pulmonary veins to left atrium.
 The increased pressure in the left atrium results in
closure of the foramen ovale. effectively
separating the two atria.
Neonatal Circulation
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2. The placental circulation ceases.
 Umbilical vessels are no longer needed they
become obliterated
 Occlusion of the placental circulation causes fall of
blood pressure in the inferior vena cava and
right atrium
3. The shunts stop to function:
 Within a day or two of birth, the ductus arteriosus
closes off, preventing blood from the aorta from
entering the pulmonary artery
 The ductus venosus closes off so that all blood
entering the liver passes through the hepatic
sinusoids.

Adult Derivatives of Fetal Vascular Structures
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 Ductus venosus becomes the ligamentum venosum,
attached to the inferior vena cava.
 Ductus arteriousus becomes ligamentum arteriousum
 Foramen ovale closes shortly after birth, fuses completely
in first year and becomes fossa ovalis
 The intra-abdominal portions of the umbilical arteries
become the medial umbilical ligaments
 The intra-abdominal portion of the umbilical vein
becomes the ligamentum teres

Persistence of Fetal Circulation
 Patent ductus arteriosus and
patent foramen ovale each
characterize about 8% of
congenital heart defects.
 Both cause a mixing of
oxygen-rich and oxygen-poor
blood
 Blood reaching tissues is not
fully oxygenated and can cause
cyanosis.
 Many of these defects go
undetected until child is at least
school age.
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THANK YOU
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1. Discuss the classification of pre-natal development
2. Write at least two Preconditions for the beginning of early
development of embryo
3. List at least 3 events that occur in the first, second and third
week of development.
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233
Quiz

General Embryology.pptx

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