1
CELL DIVISION
(A) MITOSIS
 The mitotic division occurs in the somatic cells for growth and repair.
 Before the somatic cell enters mitosis, each chromosome (which was
originally formed of two strands of DNA connected by a centromere or
kinetochore) replicates itself so that the chromosomal material is
doubled, and each replicated chromosome is now formed of two
chromatids connected by the centromere or kinetochore (Fig. 1). Each
chromatid is formed of an original strand of DNA and its replica.
During the DNA replication (interphase) the chromosomes are
extremely long, take the shape of a network, called the chromatin
network, and the individual chromosomes cannot be seen by the light
microscope.
A chromosome
formed of two
strands of DNA
Separation
of the two
strands
A replicated chromosome
formed of two chromatids
Fig. 1: DNA replication during the interphase.
 Steps of mitosis (Fig. 2):
(1) Prophase
The chromosomes begin to coil thus become shorter and thicker.
(2) Prometaphase
- The chromosomes continue coiling and shortening and they
become distinguishable, each is formed of two chromatids
2
connected at the centromere. Each chromosome has a similar one
which carries the same genetic characters. The pair of identical
chromosomes is called homologous chromosomes. Each somatic
cell is said to have 2n chromosomes, where n (haploid number) is
the number of the pairs of homologous chromosomes, and 2n
(diploid number) is the total number of chromosomes in the cell.
- The nuclear membrane begins to disappear. The centriole divides
into two, and each one of them begins to migrate towards one pole
of the cell. Microtubules (spindle) extend between the two
centrioles.
(3) Metaphase
- The chromosomes become arranged in the equatorial plane of the
cell and the chromatids are clearly visible. The chromosomes
become attached to the spindle at the centromeres.
- The nuclear membrane disappears.
(4) Anaphase
The centromere of each chromosome divides and the spindle fibers
contract withdrawing the chromatids to the opposite poles of the cell.
(5) Telophase
- The cell divides gradually into two daughter cells. The
chromosomes uncoil and lengthen to form a chromatin network.
- The nuclear membrane reforms.
- Each daughter cell receives one-half of the doubled chromosomal
material and thus, maintains the same chromosomal material and
number of the mother cell.
3
DNA
replication
2n
Interphase
Prophase
Metaphase
Prometaphase
2n
2n
Anaphase
Telophase
Fig. 2: Steps of mitosis.
4
(B) MEIOSIS

The meiotic (reduction) division occurs in the germ cells during the
production of gametes. The meiotic division consists of two stages; each
of five phases.
 First stage of meiosis (first meiotic division) (Fig. 3)
- Before the germ cell enters the first meiosis, each chromosome
replicates itself so that the chromosomal material is doubled, and each
replicated chromosome is now formed of two chromatids connected
by the centromere. Each chromatid is formed of an original strand of
DNA and its replica.
- Steps of first meiosis
(1) Prophase
- The chromosomes begin to coil thus become shorter and thicker.
- The chromosomes show two characteristic features that differ
from mitosis:
a) Pairing of the homologous chromosomes, thus form together
a tetrad formed of four chromatids.
b) Crossing over (chiasma formation) and exchange of parts
between the inner chromatids of the homologous
chromosomes (Fig. 4).
(2) Prometaphase
The same events as the prometaphase of mitosis.
(3) Metaphase
The tetrads become arranged in the equatorial plane of the cell
and the chromosomes become attached to the spindle at the
centromeres.
(4) Anaphase
The spindle fibers contract (without division of the centromeres)
withdrawing each set of homologous chromosomes towards one
pole of the cell.
(5) Telophase
The same events as the telophase of mitosis. Each daughter cell
receives half the number of chromosomes. However, as each
chromosome is duplicated, each daughter cell contains the same
amount of genetic material as the mother cell.

Second stage of meiosis (second meiotic division) (Fig. 3)
It looks exactly similar to mitosis but is not preceded by
chromosomal replication because they are already duplicated. The 23-
5
double structured chromosomes divide at the centromeres, and each of
the newly formed daughter cells receives 23 chromatids, and the
amount of the DNA in the newly formed cells is now half that of the
normal somatic cell. During production of female gametes, one of the
daughter cells of the first meiosis is large while the other is small and
called the first polar body. During the second meiosis, the large cell
gives a daughter large cell (ovum) and a polar body, while the first
polar body gives two daughter polar bodies. The three polar bodies
later on degenerate, thus during meiosis, the original mother germ cell
produces one ovum only.
Meiosis produces gametes of haploid number of chromosomes (Fig.
5) so that union of a male and a female gametes during fertilization
results in a diploid zygote.
6
DNA
replication
2n
Interphase
Meiosis I
Prophase
Metaphase
Prometaphase
n
n
Telophase
Anaphase
Interphase without
DNA replication
n
n
n
Meiosis II
(as mitosis)
n
n
Fig. 3: Steps of meiosis
7
Fig. 4: Crossing over during meiosis
Fig. 5: The result of meiosis
 Abnormal meiosis
Non separation of a pair of homologous chromosomes (nondisjunction) during anaphase of either the first or second meiosis may
occur in some cases especially with advanced mother's age. As a result
of non disjunction, one cell receives 24 chromosomes and the other 22
chromosomes instead of the normal 23 chromosomes. Fertilization of
an abnormal gamete with a normal gamete of 23 chromosomes results
in an individual of either 47 chromosomes (Trisomy) or 45
chromosomes (Monosomy).
8
GAMETOGENESIS
Spermatogenesis
 The primordial germ cells arise in the wall of the yolk sac at the end of
the 3rd week after fertilization. They reach the developing gonads at the
end of the 5th week or the beginning of the 6th week.
 At puberty, the primordial germ cells differentiate into spermatogonia
which soon begin the process of spermatogenesis to produce sperms.
 The steps pf spermatogenesis (Fig. 7)
- The spermatogonia undergo mitosis to give daughter spermatogonia.
The daughter spermatogonia are of two types :
(1) Type A: They remain as a continuous reserve for the stem cells.
(2) Type B: They differentiate into cells called primary spermatocytes.
- The 1ry spermatocytes (2n) undergo the 1 st meiotic division to
give haploid cells called 2ry spermatocytes (n).
- The 2ry spermatocytes undergo the 2 nd meiotic division. Each 2ry
spermatocyte gives two haploid cells called spermatids (n).
- The spermadits pass through a series of changes called
spermiogenesis to be transformed into sperms. These changes
include:
(1) Formation of the acrosome which extends over half the
nuclear surface and contains enzymes to assist in penetration
of the ovum and its surrounding layers during fertilization.
(2) The nucleus occupies most of the head.
(3) Formation of a neck, middle piece (contains mitochondria)
and a long tail.
(4) Shedding of most of the cytoplasm.
N.B.: In humans, the time required for a spermatogonium to develop
into mature sperms is about 64 days.
 Abnormal sperms
- About 10% of sperms may be abnormal without any loss of fertility.
However, when this ratio rises to 25% or more, fertility is usually
impaired.
- The abnormalities of the sperms may include:
1. Abnormalities in the shape of the sperms:
- Double head or double tail.
- Giant or dwarf sperms.
- Fused sperms.
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2. Abnormalities in the motility of the sperms.
3. Decrease in the total sperm count.
 Regulation of spermatogenesis (Fig. 6):
Spermatogenesis is regulated by the following pituitary hormones:
1. Luteinizing hormone (LH): It binds to receptors on Leydig cells and
stimulates testosterone production, which in turn binds to
intracellular receptors of Sertoli cells to promote spermatogenesis.
2. Follicle stimulating hormone (FSH). It binds to Sertoli cells and
stimulates synthesis of intracellular androgen receptor proteins.
Fig. 6: Regulation of spermatogenesis.
10
Fig. 7: Spermatogenesis
11
Oogenesis
 The primordial germ cells arise in the wall of the yolk sac at the end of
the 3rd week after fertilization. They reach the developing gonads at the
end of the 5th week or the beginning of the 6 th week. Immediately, the
primordial germ cells differentiate into oogonia that soon differentiate
into 1ry oocytes. Each 1ry oocyte becomes surrounded by flat epithelial
cells known as follicular cells that originate from the surface epithelium
of the ovary. The 1ry oocyte together with the surrounding follicular
cells are known as the primordial follicle. The 1ry oocytes begin the 1st
meiotic division but remain in the prophase of the 1st meiosis and do not
finish the 1st meiotic division before puberty is reached. This is probably
because of the secretion of an inhibitory substance from the follicular
cells called the oocyte maturation inhibitor (OMI). This long resting
period that extends from the 6th week of pregnancy till the age of
puberty is called the diplotene stage.
 At puberty, 5-15 primordial follicles begin to mature every month, but
one of them only completes the process of maturation. The process of
maturation involves the 1ry oocyte as well as the surrounding
follicular cells.
 Maturation of the 1ry oocyte.
(1) Maturation of the primary oocyte (Fig. 8)
The primary oocyte (which is in the prophase stage of the 1 st
meiosis) completes the 1st meiosis to give two haploid (n) cells; one
of them is large and called the 2ry oocyte and the other is small and
called a polar body. Both cells begin the 2nd meiotic division till the
metaphase stage. Ovulation occurs at this stage, where the 2ry oocyte
together with the polar body are shed from the ovary to the Fallopian
tube. During fertilization, the 2ry oocyte and the polar body
complete the 2nd meiosis where the 2ry oocyte gives a mature ovum
and a polar body, while the 1st polar body gives two polar bodies.
The three resultant polar bodies then degenerate. If no fertilization
occurs, the 2ry oocyte and the 1st polar body degenerate
approximately 24 hours after ovulation.
(2) Maturation of the follicular cells (Fig. 8)
- The follicular cells change from flat to cuboidal, then proliferate
to produce a stratified epithelium of granulose cells. The follicle
is now called the 1ry follicle. The surrounding stromal cells of the
ovary form a layer around the granulose cells known as theca
folliculi. The granulose cells secrete a glycoprotein substance that
12
deposits on the surface of the oocyte to form a layer called the
zona pellucida.
- As development continues, fluid-filled spaces appear between the
granulosa cells, and when these spaces coalesce, an antrum is
formed. At the same time, the theca folliculi become organized
into an inner layer of secretory cells known as theca interna, and
an outer layer of connective tissue known ad theca externa, and
the follicle is called now the secondary follicle. With
accumulation of fluid in the follicular antrum, the follicle
markedly increases in size till reaches about 25 mm in diameter
(originally 120µ). The theca interna becomes highly vascularized.
The granulosa cells surrounding the oocyte are called cumulus
oophorus. The follicle is now known as the Graafian, or vesicular,
follicle.
- When the Graafian follicle ruptures (ovulation), the oocyte,
together with the zona pellucida and some of the cells of the
cumulus oophorus known as corona radiata, are shed from the
ovary to the Fallopian tube waiting for fertilization.
Before labor
Primordial follicle
1ry oocyte in
prophase
of 1st meiosis
Oogonium
Primordial germ cell
Primordial follicle
Flat follicular cells
Diplotene stage
At puberty
Cuboidal follicular cells
Zona pellucida
Completion of 1st meiosis
2ry oocyte
Primary follicle
Polar body
Theca folliculi
Granulosa cells
Secondary follicle
2ry oocyte in metaphase
of 2nd meiosis
Ovulation
Follicular antrum
Fertilization
Cumulus oophorus
2ry oocyte
Mature fertilized ovum
3 polar bodies (degenerate)
Theca externa
Graafian follicle
Fig.8: Oogenesis
13
CYCLIC CHANGES WHICH OCCUR IN
THE FEMALE DURING HER
REPRODUCTIVE PERIOD
At the time of puberty, the female begins to undergo regular monthly
cycles.
During a month, the ovary changes its hormonal output (ovarian cycle)
under control of hormones secreted by the anterior lobe of the pituitary
gland (pituitary gonadotropins which are in turn controlled by hormones
secreted by the hypothalamus (gonadotropin-releasing hormones). The
endometrium, which is the mucus lining of the uterus, is very sensitive to
the ovarian hormones and it responds to these hormones by thickening and
increased vascularity so as to be ready every month to receive an embryo.
If no pregnancy occurs, the thickened endometrium is shed in the form of a
gush of blood called menstruation, and the cycle is repeated in the next
month (menstrual cycle)
Ovarian cycle
Preovulatory phase (Follicular phase)
At the beginning of each cycle, the follicular cells, which secrete the
estrogen hormone, are small and flat so the amount of estrogen in the blood
is minimal. The anterior lobe of the pituitary gland secretes the follicle
stimulating hormone (FSH) that stimulates the growth and proliferation of
the follicular cells which, thus, produce increasing amounts of estrogen.
14
The maximum amount of estrogen is reached at the stage of Graafian
follicle.
Ovulation
The high amount of estrogen stimulates the anterior lobe of the
pituitary gland to:
1. Stop the secretion of the follicle stimulating hormone (FSH.).
2. Secretion of the luteinizing hormone (LH). This hormone has the
following effects:
a) It increases the collagenase activity resulting in digestion of the
collagen fibers surrounding the follicle.
b) It increases the prostaglandin levels and this stimulates local
muscular contractions in the ovarian wall. These contractions extrude
the oocyte, together with the zona pellucida and some of the cells of
the cumulus oophorus known as corona radiata, outside the ovary.
Postovulatory phase (Luteal phase)
Following ovulation, the remaining granulosa cells and the theca
interna cells develop yellowish pigment (luteinization) under the influence
of the LH and change into lutean cells which form the corpus luteum that
secretes increasing amounts of the hormone progesterone
If fertilization does not occur, the corpus luteum reaches its maximum
development about 9 days after ovulation. By that time, the blood contains
the maximum amount of progesterone. The high level of progesterone
stimulates the anterior lobe of the pituitary gland to stop its LH secretion.
This leads to gradual degeneration of the corpus luteum which is finally
transformed into a mass of fibrous tissue called the corpus albicans with
subsequent drop of the progesterone level in the blood.
Uterine (Menstrual) cycle
Proliferative phase (Postmenstrual phase) (Estrogen phase)
It corresponds to the preovulatory phase of the ovarian cycle. Under
the effect of estrogen, the endometrium becomes thickened with
enlargement of its blood vessels and mucus glands. This phase lasts for
about 10 days.
Secretory phase (Premenstrual phase) (Progestational phase)
It corresponds to the postovulatory phase of the ovarian cycle. Under
the effect of progesterone, the endometrium becomes markedly thickened
and its 3 histological layers (superficial compact, intermediate spongy and
15
the basal layers) are identified. The arteries become markedly enlarged and
twisted so called spiral arteries. The mucus glands become enlarged and
full of secretions. This phase lasts for 14 days.
Menstrual phase
With degeneration of the corpus luteum and the drop of the
progesterone level, the endometrium degenerates and is expelled from the
uterus in the form of bleeding containing mucus and pieces of mucus
membrane (menstrual blood), and the basal layer is the only part of the
endometrium which is retained. This phase lasts for about 4 days.
If pregnancy occurs, the corpus luteum (called the corpus luteum of
pregnancy) is maintained by a hormone called chorionic gonadotropin
secreted by the chorion. The corpus luteum remains the source of
progesterone secretion till the end of the 4th month of pregnancy when it
degenerates. After the 4th month of pregnancy, the placenta takes the role of
progesterone secretion. The first day of menstruation is considered as the
first day of the menstrual cycle.
Fig. 9: Changes in the endometrium and corresponding changes in the
ovary during a regular menstrual cycle.
16
FIRST WEEK OF DEVELOPMENT
Fertilization
 Definition: Fertilization is the union of the sperm and the ovum to form
the zygote.
 Site: In the ampulla of the Fallopian tube.
 Mechanism (Fig. 10):
Of the 200 to 300 million sperms deposited in the female genital tract,
only 300 to 500 reach the site of fertilization These sperms are not able
to fertilize the oocyte immediately and must undergo certain changes to
acquire this capability. These changes include:
1- Capacitation and penetration of the corona radiata:
Many of the sperms that reach the site of fertilization undergo a
process called capacitation which includes removal of the
glycoprotein coat and the seminal plasma proteins that overlie the
acrosomal region of the sperm. Only capacitated sperms can pass
freely through the corona radiata. The process of capacitation lasts
for about 7 hours.
2. Penetration of the zona pellucida:
The zona pellucida which is a glycoprotein shell surrounding the egg
contains sperm binding sites. When the capacitated sperms bind to
the zona pellucida, they begin to secrete acrosomal enzymes that
allow one of these sperms to penetrate the zona (acrosome reaction),
thus the head of this sperm comes in contact with plasma membrane
of the oocyte.
3. Fusion of the fertilizing sperm and the oocyte:
The plasma membranes of the head of the sperm and that of the
oocyte adhere, and both the head and tail of the sperm enter the
cytoplasm of the oocyte leaving the plasma membrane outside the
oocyte. As soon as the sperm has entered the oocyte, the egg
responds in the following ways:
a) Cortical and zona reactions:
Release of lysosomal enzymes from cortical granules lining the
plasma membrane of the oocyte results in:
- The oocyte membrane becomes impermeable to other sperms.
- The sperm binding sites of the zona pellucida are changed so
that no more sperms can bind to the zona
17
b) Completion of the second meiotic division of the 2ry oocyte that
gives a mature fertilized ovum and a polar body which later
degenerates.
c) The nucleus of the ovum (female pronucleus) fuses with the
nucleus of the sperm (male pronucleus) to form the nucleus of
the zygote. The tail of the sperm is detached and degenerates.
Fig. 10: Fertilization
 Results:
1. Restoration of the diploid number of chromosomes, half from the
father and half from the mother. Hence, the zygote contains a new
combination of chromosomes different from both parents.
2. Determination of the sex of the new individual. An X-carrying sperm
produces a female (XX) embryo, and a Y-carrying sperm produces a
male (XY) embryo.
3. Initiation of cleavage.
 Laboratory techniques of artificial fertilization:
1. In vitro fertilization (IVF):
This technique is now of frequent practice conducted by many
laboratories through the world. It is useful to overcome either male
infertility (as a result of insufficient number of sperms and/or poor
motility) or female infertility (as a result of tubal obstruction, hostile
cervical mucus, immunity to sperms, absence of ovulation or others).
18
Follicle growth in the ovary is stimulated by administration of
gonadotropins. Oocytes are withdrawn from the ovarian follicles
with an aspirator just before ovulation when the oocyte is in the late
stages of 1st meiosis. The egg is placed in a culture medium and the
sperms are added immediately. When the fertilized eggs reach the 8cell stage, they are implanted into the uterus to develop to term
2. Intracytoplasmic sperm injection (ICSI):
In this technique a single sperm is injected into the cytoplasm of the
egg to cause fertilization.
Cleavage
 After 24 hours, the zygote undergoes a mitotic division to give a twocell stage. After another 24 hours, a second mitotic division occurs to
give a four cell stage.
 Morula formation:
The zygote undergoes a series of mitotic divisions, resulting in a rapid
increase in the number of cells. These cells, which become small with
each cleavage division, are known as blastomeres. At 16 cell stage, the
zygote becomes similar in appearance to a mulberry and is known as
morula.
 Blastocyst formation:
- The morula reaches the uterine cavity at the end of the 4 th day or
beginning of the 5th day after fertilization.
- The zona pellucida disappears at about the end of the 5th day after
fertilization.
- Fluid begins to penetrate through the zona pellucida into the
intercellular spaces of the morula. Gradually, the intercellular spaces
become confluent and finally a single cavity called the blastocele is
formed. At this time, the embryo is known as blastocyst. The cells of
the blastocyst are arranged into an inner cell mass (embryoblast) and
an outer cell mass (trophoblast). The pole of the blastocyst at which
the embryoblast lies is called the embryonic pole and the other pole
is called the abembryonic pole.
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Migration
The zygote is transported from the site of fertilization in the ampulla of the
Fallopian tube to the uterine cavity by two mechanisms:
1. The muscular peristalsis of the Fallopian tube.
2. The ciliary action of the ciliated epithelium of the Fallopian tube.
Implantation
- Definition: It is the process by which the blastocyst penetrates the
superficial compact layer of the endometrium.
- Time: Begins about the 7th day after fertilization and is completed about
the 11th day.
- Site: Usually in the upper part (fundus) of the uterus.
- Mechanism: The erosion of the epithelial cells of the mucosa results
from proteolytic enzymes produced by the trophoblast at the embryonic
pole.
- Abnormal sites of implantation:
1. Implantation in the lower segment of the uterus close to the internal
os. At later stages of development, the placenta overlies the os
(placenta previa). This case may lead to severe bleeding in late
pregnancy or during delivery and the baby may suffer from asphyxia
during labor.
2. Extrauterine implantation:
- Tubal implantation: The tube ruptures at about the 2nd month of
pregnancy resulting in severe internal hemorrhage.
- Implantation at any place in the abdominal cavity or the wall of the
ovary.
20
Day 3
Day 1
Day 5
Morula
Zona pellucida
Ovary
Blastocyst
Trophoblast
Embryoblast
Day 7
Implanted blastocyst
Endometrium
Day 11
Blastocyst
Fig. 11: The events during the first week of development
21
SECOND WEEK OF DEVELOPMENT
8th day of development
 The blastocyst is partially embedded in the endometrium.
 The trophoblast differentiates into
1. Syncytiotrophoblast: An outer multinucleated layer without distinct
cell boundaries.
2. Cytotrophoblast: An inner layer of multinucleated cells with clear
cell boundaries.
 The embryoblast differentiates into:
1. Epiblast: A layer of tall columnar cells adjacent to the
cytotrophoblast.
2. Hypoblast: A layer of small cuboidal cells adjacent to the blastocele.
The embryoblast is called now the bilaminar germ disc.
 Cavity formation:
A cavity called the amniotic cavity appears within the epiblast. The
epiblast cells adjacent to the cytotrophoblast are called amnioblasts
which form the roof of the amniotic cavity, while its floor is formed of
the rest of the epiblast..
9th&10th days of development
 The blastocyst is more deeply embedded in the endometrium and the
penetration defect in the surface epithelium is closed by a fibrin clot.
 The trophoblast:
Vacuoles appear in the syncytiotrophoblast particularly at the
embryonic pole. When these vacuoles fuse, they form large lacunae.
 Cavity formation:
A layer of flat cells arise from the hypoblast and form a membrane
called Heuser's (exocoelomic) membrane which lines the inner surface
of the cytotrophoblast. The original blastocele is now called the 1ary
yolk sac (exocoelomic cavity) whose roof is the hypoblast and its floor
is Heuser's membrane.
11th&12th days of development
 The blastocyst is completely embedded in the endometrium, and the
penetration defect in the surface epithelium is almost healed by
epithelialization.
22
 The trophoblast
- Syncytiotrophoblast:
The syncytial cells penetrate deeper into the endometrium and erode
the endothelial lining of the maternal sinusoids thus blood flows
through the lacunae establishing the uteroplacental circulation..
- Cytotrophoblast:
A new population of cells arises from the inner surface of the
cytotrophoblast. These cells form fine loose tissue called the
extraembryonic mesoderm that covers the amniotic cavity and the
1ary yolk sac. The trophoblast and the extraembryonic mesoderm are
called together the chorion, and the whole vesicle is called the
chorionic sac or the chorionic vesicle. . Soon, large cavities develop
in the extraembryonic mesoderm and when these spaces fuse, a new
space known as the extraembryonic coelom or chorionic cavity is
formed. The extraembryonic coelom divides the extraembryonic
mesoderm into two layers: extraembryonic somatopleuric mesoderm
that lines the cytotrophoblast, and extraembryonic splanchnopleuric
mesoderm that covers the 1ary yolk sac. However, the
extraembryonic coelom does not extend in certain region at the roof
of the amniotic cavity where the germ disc is connected to the
trophoblast by the connecting stalk.
13th&14th days of development
 The surface defect in the endometrium has usually healed. Occasionally,
however, bleeding occurs at the implantation site as a result of the
increased blood flow into the trophoblastic trabeculae. Because this
bleeding occurs near the 28th day of the menstrual cycle, it may be
confused with normal menstrual bleeding and, therefore, causes
inaccuracy in determining the expected delivery date.
 The trophoblast:
Cells of the cytotrophoblast proliferate and penetrate into the
syncytiotrophoblast, thus forming cellular columns surrounded by
syncytium. The cellular columns with the syncytial covering are called
the 1ary chorionic villi.
 Cavity formation:
With enlargement of chorionic cavity, the 1ary yolk sac is pinched off
and thus transformed into a smaller cavity called 2ary yolk sac.
23
N.B.: The second week is sometimes called the week of twos because:
1. The trophoblast differentiates into two layers; Syncytiotrophoblast
and cytotrophoblast.
2. The embryoblast differentiates into two layers; the epiblast and the
hypoblast.
3. The extraembryonic mesoderm is divided into two layers;
somatopleuric and splanchnopleuric layers.
4. There are two cavities related to the embryoblast; the amniotic
cavity and the yolk sac.
Fig. 12: The events during the second week of development
24
THIRD WEEK OF DEVELOPMENT
A- Development of the germ disc
1- Gastrulation (Formation of a trilaminar germ disc)
 Formation of the primitive streak
The cells of the epiblast in the middle region of the disc close to its
caudal end proliferate to form a cord of cells called the primitive
streak (Fig. 13). The streak appears on the surface of the epiblast as a
narrow groove with slightly raised regions on either side. The
cephalic end of the streak forms a bulge known as the primitive node
which is represented on the surface of the epiblast by a depression
called the primitive pit.
 Formation of the three germ layers (endoderm, mesoderm and
ectoderm)
- Cells of the primitive streak detach from the epiblast and slip
beneath it. This inward movement is known as invagination (Fig.
13).
- Once the cells have invaginated, some displace the hypoblast
creating the embryonic endoderm, and others come to lie between
the epiblast and the newly created endoderm to form the
intraembryonic mesoderm. The cells remaining in the epiblast
form the ectoderm, and the amnioblasts are now attached to the
ectoderm along the margins of the disc (amnio-ectodermal
junction). Thus, the epiblast, through the process of gastrulation,
is the source of all the germ layers which will give rise to all
tissues and organs of the embryo.
Fig. 13: Invagination of the cells of the primitive streak
25
2. Spread and differentiation of the intraembryonic mesoderm
- The cells of the intraembryonic mesoderm arising from the primitive
streak spread in all directions between the ectoderm and the
endoderm except in three regions (Fig. 14):
1- A region near the cephalic end where the prechordal plate
(enlarged endodermal cells) is firmly attached to the overlying
ectodermal cells and both form an ectoendodermal membrane
called the buccopharyngeal membrane.
2- A region just caudal to the primitive streak where the ectoderm
and the endoderm are firmly attached to form an ectoendodermal
membrane called the cloacal membrane.
3- The middle region of the disc between the primitive node and the
buccopharyngeal membrane because this region is occupied by
the notochord.
- Gradually the cells of the intraembryonic mesoderm migrate beyond
the margins of the disc and establish contact with the extraembryonic
mesoderm covering the yolk sac and the amnion (Fig. 14).
- By approximately the 17th day, the intraembryonic mesoderm
become differentiated into three columns: paraxial, intermediate and
lateral plate mesoderm (Fig. 15).
- The lateral plate mesoderm extends in the cephalic region of the disc
cranial to the buccopharyngeal membrane. Small cavities appear in
the lateral plate mesoderm, and when these cavities coalesce they
form a single cavity within the lateral plate mesoderm called the
intraembryonic coelomic cavity. This cavity divides the lateral plate
mesoderm into two layers: a somatic layer which is continuous with
the extraembryonic mesoderm which covers the amnion, and a
splanchnic layer which is continuous with the extraembryonic
mesoderm which covers the yolk sac.
The intraembryonic coelomic cavity is a U-shaped cavity (Fig. 15)
that extends on the sides of the disc, and its cranial part, called the
pericardial cavity, lies cranial to the buccopharyngeal membrane. On
each side of the disc, the intraembryonic coelomic cavity is
continuous with the extraembryonic coelom. However, in the most
cephalic part of the disc there is a mass of mesoderm called the
septum transversum in which the intraembryonic coelom does not
extend.
26
Fig. 14: Formation of the intraembryonic mesoderm.
Fig. 15: Differentiation of the intraembryonic mesoderm.
27
3. Formation of the notochord (Fig. 16)
- Prenotochordal cells:
Invagination of the cells of the primitive pit results in the formation
of a tube-like process called the prenotochordal process that extends
in the middle region of the disc between the primitive node and the
buccopharyngeal membrane.
- Notochordal-endodermal fusion:
The tube of prenotochordal cells fuses with the underlying
endoderm.
- Neurenteric canal:
Degeneration of the notochordal-endodermal junction leads to
formation of a temporarily passage between the amniotic cavity and
the yolk sac, this passage is called the neurenteric canal. The roof of
the canal is a curved plate of the remaining portion of the
prenotochordal cells intercalated in the endodermal germ layer. This
plate is called the notochordal plate.
- Definitive notochord
- The notochordal plate becomes detached from the endoderm, and is
folded around its longitudinal axis to form a solid cord known as the
definitive notochord. The endodermal cells proliferate to form once
again an uninterrupted layer in the roof of the yolk sac. The
notochord now forms a temporarily midline axis that will be replaced
later by the permanent axial skeleton.
28
Fig. 16: Development of the notochord
4. Growth of the germ disc
- Initially, the germ disc is flat and almost round. Gradually, it
becomes pear-shaped with broad cephalic and narrow caudal ends.
The expansion of the disc, especially in the cephalic region, is due to
the continuous migration of the cells of the primitive streak mainly in
the cephalic direction.
- Migration of the cells of the primitive streak to the cephalic region of
the disc stops about the middle of the 3 rd week, while the process
continues in the caudal part of the disc till the end of the 4 th week.
Accordingly, the germ layers in the cephalic part of the disc begin
their specific differentiation by the middle of the 3 rd week, whereas
in the caudal part this occurs by the end of the 4 th week. Thus
gastrulation or the formation of the germ layers, continues in caudal
segments while cranial structures are differentiating causing the
embryo to develop cephalocaudally.
29
B- Development of the trophoblast
 Primary chorionic villi
The 1ry chorionic villi appear by the end of the 2 nd week of
development. By the beginning of the 3 rd week, more 1ry chorionic villi
are formed especially at the embryonic pole. The 1ry chorionic villus
consists of a cytotrophoblastic core covered by a syncytial layer.
 Secondary chorionic villi
During the 3rd week of development, extraembryonic mesoderm invades
the cores of the 1ry villi to form 2ry chorionic villi. The 2ry villus is
formed of a core of mesoderm covered by cytotrophoblast then
syncytiotrophoblast.
 Tertiary chorionic villi
- By the end of the 3rd week of development, the mesodermal cells in
the cores of the 2ry villi begin to differentiate blood cells and small
blood vessels, thus forming a villous capillary system. The villi now
are called tertiary chorionic villi.
- The capillaries in the 3ry villi make contact with capillaries
developing in the wall of the chorion and in the connecting stalk.
These vessels in turn establish contact with the intraembryonic
circulatory system, thus when the heart begins to beat in the 4 th week
of development, the fetal blood enters the villous capillary system.
Exchange of nutrients, wastes and gases occurs between the fetal
blood in the villous capillary system and the maternal blood in the
intervillous space.
 Outer cytotrophoblastic shell
- The cytotrophoblastic cells in the villi penetrate progressively into
the overlying syncytium until they reach the maternal endometrium
where they establish contact with similar extensions of neighboring
villi, thus forming an outer cytotrophoblastic shell. This shell
gradually surrounds the trophoblast entirely and attaches the
chorionic sac firmly to the maternal endometrial tissue.
- The villi that extend from the surface of the chorionic sac to the
cytotrophoblastic shell are called the stem or anchoring villi, while
the villi that branch from the sides of the stem villi are called the free
or terminal villi.
30
Fig. 17: Development of the chorionic villi
31
EMBRYONIC PERIOD
FOURTH TO EIGHTH WEEK OF
DEVELOPMENT
During this period each of the three germ layers; ectoderm, mesoderm and
endoderm gives rise to a number of specific tissues and organs so that by
the end of this period the main organs and systems have been established so
this period is called the period of organogenesis. Furthermore, the shape of
the embryo greatly change during this period and the major features of the
external body form are recognizable by the end of the second month
A- Development of the three germ layers
Development of the ectoderm
 The general development of the central nervous system (Neurulation)
- Neural plate:
Appearance of the notochord induces the middle region of the
overlying ectoderm to thicken and form the neural plate
(neuroectoderm).
- Neural groove & neural folds and neural crests
The neural plate becomes invaginated to form a neural groove. The
elevated edges of the neural groove are called the neural folds. A strip
of modified ectodermal cells, called neural crest, appears on each side
of the neuroectoderm.
- Neural tube:
With deepening of the neural groove, the neural folds gradually
approach each other till they fuse to from a neural tube. The fusion
begins in the region of the future neck then proceeds in cephalic and
caudal directions. Initially, the neural tube has two openings called
anterior and posterior neuropores which are later closed at days 25 &
27 respectively. The cephalic part of the neural tube becomes
expanded to form the brain vesicle, while its caudal part remains
narrow and will give rise to the spinal cord.
- Development of the neural crests:
With deepening of the neural groove, the neural crests are
approximated then fuse together and become separated from the
surface ectoderm and the neuroectoderm. Soon they separate again to
form two strips beneath the ectoderm and lie on the dorsolateral aspect
32
of the neural tube. Later they become segmented and their cells
migrate in different directions to give many derivatives.
- Otic placode and lens placode:
By the time the neural tube is closed, two other ectodermal thickenings
called the otic and lens placodes become visible in the cephalic region
of the embryo. During further development, the otic placode
invaginates and forms the otic vesicle which will develop into the
internal ear. The lens placode also invaginates to form the lens of the
eye.
Fig. 18: Early development of the neuroectoderm
 The ectoderm gives rise to the following structures:
1- The central nervous system: The brain and the spinal cord.
2- The peripheral nerves: spinal and cranial.
3- The sensory epithelia of the ear nose and eye.
4- The epidermis of the skin including the hairs, nails and sebaceous
and sweat glands.
5- The pituitary gland.
6- The mammary gland.
7- The anterior part of the oral cavity including the enamel of the teeth.
8- The lower half of the anal canal.
9- The lower part of the male urethra.
10- Derivatives of the neural crests:
a. Arachnoid and pia maters.
33
b.
c.
d.
e.
f.
g.
h.
i.
j.
k.
Schwann cells of the peripheral nerves.
Glial cells
Dorsal root ganglia of the spinal nerves.
Sensory ganglia of cranial nerves.
Autonomic ganglia.
Medulla of adrenal gland.
Melanocytes.
C cells of thyroid gland.
Some bones of the face and skull.
Conotruncal septum of the heart.
Development of the intraembryonic mesoderm
 Paraxial mesoderm
- The paraxial mesoderm is segmented into blocks called somitomeres
which first appear in the cephalic region of the embryo, and their
formation proceeds cephalocaudally. In the head region, the
somitomeres are 7 in number and they form muscles in the head and
neck. From the occipital region caudally, the somitomeres are called
somites (Fig. 19).
- The first pair of somites appears in the occipital region at approximately
the 20th day, then new somites appear in a cephalocaudal sequence,
approximately 3 per day till the 30th day when the number of somites is
about 31. Formation of somites continues at a slower rate till 35th or
40th day, however the newly formed somites after the 30 th day are small
and hardly visible. Since the easily visible somites are formed from the
20th till the 30th day, this period is called the somite period.
20 21 22 23 24 25 26 27 28 29 30
Age in
days
1
4
7 10 13 16 19 22 25 28 31
Number
of
somites
Table 1: Number of somites correlated to approximate age in days
If you are given the number of somites, and you are asked to determine
the age of the embryo, apply this equation
Age of the embryo= (number of somites - 1) / 3 + 20
34
- Regional classification of somites:
The total number of somites is 42-44. They are distributed in the
different regions as follows:
4
occipital
8
cervical
12
thoracic
5
lumbar
5
sacral
8-10 coccygeal
- Differentiation of the somite (Fig. 19):

Each somite divides into a ventromedial part called sclerotome and a
dorsolateral part called dermomyotome

The cells of the sclerotome form a loose tissue called mesenchyme
that surrounds the spinal cord and the notochord to from the vertebral
column.

The dermomyotome differentiates into a dermatome and a myotome.
The dermatomes form the dermis of the skin, while the myotomes
give the striated muscles of the limbs and the body wall. Since each
somite has its own nerve supply, the muscles and skin arising from a
somite are innervated by the nerve of this somite (segmental nerve
supply of muscles and skin).
Fig. 19: Development of the intraembryonic mesoderm
35
 Intermediate mesoderm
- In the cervical and upper thoracic regions it is segmented into small
mesodermal clusters, while more caudally it forms an unsegmented
mass called the nephrogenic cord.
- It gives rise to the kidneys, ureters and genital structures in the male.
 Lateral plate mesoderm
1- The parietal (somatic) mesoderm:
It forms the connective tissue of the lateral and ventral body wall as
well as the parietal layers of the serous membranes (peritoneum,
pleura and pericardium). It also gives rise to the Fallopian tubes,
uterus and most of the vagina.
2- The visceral (splanchnic) mesoderm:
It forms the smooth muscles and connective tissue of the gut and
respiratory organs & the cardiac muscle and the visceral layers of the
serous membranes.
Development of the endoderm
It gives:
1- Epithelial lining of:
a) Gastrointestinal tract (except the anterior part of the mouth cavity
and the lower half of the anal canal).
b) Respiratory tract.
c) Most of the urinary bladder and urethra.
d) The tympanic cavity and the Eustachian tube.
2- Parenchyma of:
a) Liver.
b) Pancreas.
c) Thyroid gland.
d) Parathyroid glands.
e) Tonsils.
f) Thymus.
36
B- Folding of the embryonic disc

Types of folds:
1. Head and tail folds:
They result from growth of the embryonic disc in a cephalocaudal
direction mainly due to the rapid longitudinal growth of the central
nervous system.
2. Lateral folds:
They result mainly by the rapidly growing somites.
 Results of folding Fig. 20):
1. The embryonic disc bulges into the amniotic cavity, and the original
flat embryo acquires a cylindrical appearance with formation of a
body cavity.
2. The amnio-ectodermal junction is shifted to the ventral side of the
body in the form of a ring called the primitive umbilical ring.
3. The connecting stalk is shifted to the ventral side of the body.
4. Formation of the gut
- The endoderm, which was originally in the form of a flat plate, is
transformed into a tube called the gut. The major part of the
original yolk sac is incorporated into the body cavity, and the
initial wide communication between the embryo and the yolk sac
becomes constricted until only a narrow duct (vitelline duct or
yolk sac stalk) remains.
- The parts of the gut in the head and tail folds are called the
foregut and hindgut respectively, while the part in between is
called the midgut. The midgut remains temporarily connected
with the yolk sac through the vitelline duct. A diverticulum of the
hindgut called the allantois protrudes into the connecting stalk.
- The buccopharyngeal and cloacal membranes lie at both ends of
the gut. When these membranes rupture, an open communication
between the gut and the amniotic cavity is established at each
end.
5. The septum transversum as well as the pericardial cavity and heart
become shifted to the ventral side of the body in front of the foregut,
and the brain becomes in the most cephalic region of the embryo.
6. The initial relation of the septum transversum, the pericardial cavity
and the buccopharyngeal membrane to each other is reversed, so
after folding the buccopharyngeal membrane becomes the most
cephalic, and the septum transversum becomes the most caudal,
while the pericardial cavity and heart remain in between.
37
7. After folding, the intraembryonic coelomic cavity surrounds the gut
and is connected anteriorly with the ventrally displaced pericardial
cavity.
Fig. 20: Folding of the embryonic disc
38
C- External appearance of the embryo during the
second month
By the end of the second month, the external features of the embryo are
greatly changed:
1. The embryo has a head, buttocks and anterior and posterior body walls.
The head is large in proportionate to the size of the body. Eyes, nose
and ears are easily identified. A mouth and anal openings can be also
seen.
2. Appearance of limbs:
- By the beginning of the 5th week, forelimbs and hindlimbs appear as
small buds. The forelimb buds appear at the level of the 4 th cervical
to the 1st thoracic somites (this explains the innervation by the
brachial plexus), while the hindlimb buds appear slightly later at the
level of the lumbar and upper sacral somites (this explains the
innervation by the lumbar and sacral plexuses).
- With further development, the terminal portion of each bud becomes
flattened and demarcated from the rest of the bud by a constriction.
Soon, four radial grooves separate five masses in the distal portion of
the bud to form the digits. These grooves appear first in the hand
region and shortly afterward in the foot.
- While the fingers and toes are being formed, a second constriction
divides the proximal portion of the bud into two segments, thus the
three parts characteristic of the adult limbs can be recognized.
3. Determination of the age of the embryo during the embryonic period:
- During the somite period, it is possible to determine the age of the
embryo by counting the number of the somites.
- Since counting the somites becomes difficult during the second
month of development, the age of the embryo is estimated by the
crown-rump (CR) length. The CR length is the measurement from
the vertex of the skull to the point between the apices of the buttocks.
CR length in
Age of embryo in
mm
weeks
5-8
5
10-14
6
17-22
7
28-30
8
Table 2: Crown-rump length correlated to
approximate age in weeks
39
Fig. 21: External features of the embryo during the 2nd month of
development
40
FETAL PERIOD
(FROM THE THIRD MONTH TILL BIRTH)





This Period is characterized by:
1. Maturation of the already formed tissues and organs,
2. Rapid growth.
The following items are considered as parameters of growth during this
period:
1. The growth in length.
2. The relative size of the head to the whole body.
3. The growth in weight.
4. The external features of the body.
5. The fetal movements.
The growth in length:
- At the end of the 3rd month, the CR length of the fetus is about 5-8
cm.
- During the 4th and 5th months, there is a rapid increase in length so
that by the end of the 5th month, the CR length reaches about 18 cm
and the CH (crown-heel) length reaches about 23 cm. The CH length
is the measurement from the vertex of the skull to the heel.
- At birth, the CR length is about 36 cm and the CH length is about 50
cm.
The relative size of the head to the whole body:
During the fetal period, there is a relative slowdown in the growth of the
head compared to the rest of the body so that:
- At the beginning of the 3rd month, the head constitutes 1/2 the CR
length.
- At the beginning of the 5th month, the head constitutes 1/3 of the CH
length.
- At birth, the head constitutes 1/4 of the CH length
The growth in weight:
- Although there is a rapid increase in length during the 4th and 5th
months, the weight gain during this period is little so that the weight
of the fetus is about 500 gm by the end of the 5th month.
- During the second half of pregnancy, the weight of the fetus
increases considerably particularly during the last 2½ months when
50% of its full term weight (approximately 3.5 kg) is added due to
deposition of subcutaneous fat.
The external features of the body:
- During the 3rd month:
41
The face becomes more human-looking. The eyes, which were
initially directed laterally, become located in the ventral aspect of
the face, and the ears come to lie close to their definite position at
the side of the head.

The limbs reach their relative length in comparison to the rest of
the body.

The external genitalia develop to such a degree that by the 12th
week the sex of the fetus can be determined by external
examination.
- During the 4th and 5th months, the fetus is covered with fine hair
called lanugo hair. The eyebrows and head hair are also visible.
- Till the end of the 6th month, the skin of the fetus is wrinkled because
of the lack of underlying connective tissue. During the last two
months, the fetus obtains well rounded contours due to deposition of
subcutaneous fat.
- Just before labor, the testes descend to the scrotum and the skin is
covered by a whitish fatty substance called vernix caseosa which is
composed of the secretory products of the sebaceous glands.

Fig. 22: External features of the body during the fetal period

The fetal movements;
- At the end of the 3rd month, reflex activity can be evoked. However,
these reflex movements are so limited and are not noticed by the
mother.
- During the 5th month, the movements of the fetus are usually clearly
recognized by the mother.
42
PLACENTA

Description of the full term placenta (Fig. 23).
- Shape: Discoid.
- Diameter: 20 cm.
- Thickness: 2 cm.
- Weight: 1/2 kg
- Surfaces:
1- Fetal surface:
It is smooth, covered with amnion, and the umbilical cord is
attached usually near its center.
2- Maternal surface:
It shows 15-20 slightly bulging areas (cotyledons) separated by
grooves.
Fig. 23: Shape of the placenta. A- Fetal surface. B- Maternal
surface
43

Components of the placenta:
It is formed of 2 components:
- Maternal component: Decidua basalis.
- Fetal component: Chorion frondosum.
A. Decidua basalis
- Decidua (Fig. 24) is the endometrium of pregnancy i.e. the
endometrium after penetration of the blastocyst. It is called
decidua, which means something shed, because it is shed during
labor.
- Parts of the decidua:
1- Decidua basalis:
It is the part of the decidua at the embryonic pole of the
blastocyst i.e. between the blastocyst and the wall of the
uterus.
2- Decidua capsularis:
It is the part of the decidua which covers the blastocyst (except
the embryonic pole) in the form of a capsule.
3- Decidua parietalis:
It is the part of the decidua which lines the uterine cavity.
- Fate of the decidua (Fig. 24):
1- Decidua basalis:
It is invaded by the chorionic villi at the embryonic pole and
both form the placenta.
2- Decidua capsularis and parietalis:
The decidua capsularis is stretched with the increase in the
size of the chorionic vesicle till it comes in contact with the
decidua parietalis with obliteration of the uterine cavity. With
increasing pressure of the enlarging chorionic vesicle, both
layers degenerate.
44
Fig. 24: Decidua
B. Chorion frondosum (Fig. 25):
In the early weeks of development, the villi cover the entire surface
of the chorion. As pregnancy advances, the villi at the embryonic
pole continue to grow and branch thus giving rise to the chorion
frondosum. On the other hand, the villi at the abembryonic pole
degenerate, and by the 3rd month this side of the chorion becomes
smooth and is known as chorion leave.
Chorion
frondosum
Chorion
leave
Fig. 25: Chorion frondosum and chorion leave
45
 Structure of the placenta (Fig. 26) :
The placenta can be divided into 3 regions:
1- Chorionic plate:
It is formed of the following structures:
a- Amnion
b- Extraembryonic mesoderm.
c- Cytotrophoblast.
d- Syncytiotrophoblast which lines the intervillous space.
2- Decidual plate:
It is formed of the following structures:
a- Syncytiotrophoblast which lines the intervillous space
b- Outer Cytotrophoblastic shell.
c- The maternal decidua basalis. During the 4 th and 5th months, the
decidua forms a number of septa (the decidual septa) which
project into the intervillous space but do not reach the chorionic
plate. Each septum has a core of maternal tissue and its surface is
covered by syncytiotrophoblast. As a result of this septa
formation, the maternal surface of the placenta is divided into a
number (15-20) of components called the cotyledons. Formation
of these septa may be a source of fixation between the two
components of the placenta because during this period (the 4 th and
5th months) the cytotrophoblast begins to degenerate, and
originally the decidua basalis was firmly attached to the outer
cytotrophoblastic shell.
3- Chorionic villi and intervillous space:
- The chorionic villi, either anchoring villi (stem villi) or free villi
(terminal villi) are bathed by the maternal blood in the
intervillous space. The intervillous space is lined by
syncytiotrophoblast.
- The barrier that separates the fetal blood circulating in the
capillaries of the chorionic villi and the maternal blood in the
intervillous space is called the placental barrier.
- Initially, the placental barrier is formed of four layers:
a- The endothelium of the capillaries inside the chorionic villi.
b- The connective (extraembryonic mesoderm) in the core of the
villus.
c- The cytotrophoblast.
d- The syncytiotrophoblast.
- During
the 4th month, the connective tissue and the
cytotrophoblast degenerate, thus the barrier becomes formed of
46
two layers only, and the endothelium of the chorionic villous
capillaries comes in intimate contact with the syncytial
membrane. This greatly increases the rate of exchange between
the fetal and maternal bloods.
DECIDUAL PLATE
CHORIONIC PLATE
Decidual septa
Fig. 26: Structure of the placenta

Placental circulation (Fig. 27) :
1- Maternal circulation:
The oxygenated blood of the spiral arteries of the endometrium is
poured into the intervillous space to bath the chorionic villi. The
blood in the intervillous space is drained back into the maternal
blood through the endometrial veins.
47
2- Fetal circulation:
The heart of the fetus pumps deoxygenated blood through two
umbilical arteries in the umbilical cord. The umbilical arteries are
connected with the chorionic vessels beneath the amnion, and with
the villous capillary system. Exchange of gases, nutrients and wastes
occurs through the placental barrier, then the oxygenated blood laden
with nutrients returns to the heart of the fetus through the umbilical
vein.
Maternal
blood in the
intervillous
space
Fetal blood in the
capillaries of the
chorionic villi
Fig. 27: Placental circulation

Functions of the placenta:
1- Exchange of gases:
Oxygen passes through the placental barrier from the maternal to the
fetal blood, while carbon dioxide diffuses in an opposite direction.
2- Exchange of nutrients and wastes:
Nutrients as amino acids, fatty acids, glucose, minerals and
electrolytes pass through the placental barrier from the maternal to
the fetal blood, while chemical wastes diffuse in the opposite
direction.
3- The placenta has a protective function to the fetus:
- It allows the passage of maternal antibodies to the fetal blood,
thus the fetus acquires passive immunity against many infectious
diseases.
- It prevents many infectious agents and chemicals in the maternal
blood to pass to the fetus. However, some viruses such as
measles, German measles, herpes simplex and cytomegalo virus
48
can pass through the placental barrier. Furthermore, most of the
drugs and many chemicals such as alcohol, nicotine, cocaine and
heroin can pass through the placental barrier and may result in
congenital malformations.
4- Production of hormones:
a- Chorionic gonadotropins:
They are produced by the syncytiotrophoblast in the first four
months of pregnancy to stimulate the corpus luteum to secrete
progesterone. These hormones are excreted in the urine of the
mother, so their presence in urine is used as an indicator of an
early pregnancy.
b- Progesterone and estrogen
They are produced by the syncytiotrophoblast by the end of the
4th month to maintain pregnancy.
c- Melanin spreading factor:
It is responsible for concentrating melanin in certain areas of the
skin, as the nipple and areola which become dark in color.
d- Somatomammotropin (placental lactogen)
- It gives the fetus priority on maternal blood glucose and makes
the mother somewhat diabetogenic.
- It promotes breast development for milk production.
 Abnormalities of the placenta (Fig. 28) :
1- Abnormalities in the shape:
Bilobed or trilobed placenta with one umbilical cord
2- Abnormalities in number:
a- Accessory placenta:
The placenta is formed of a large and a small parts which share
one umbilical cord. The small part may be retained after shedding
of the large part during labor, and this causes severe haemorrhage
after labor.
b- Twin placenta:
Presence of two placentae, each has its own umbilical cord. This
occurs in presence of twins.
3- Abnormalities regarding the attachment of the umbilical cord:
The umbilical cord is usually attached to the center of the fetal
surface of the placenta (centric attachment) or near the center
(eccentric attachment). The abnormalities include:
a. Marginal attachment (Battledore placenta): The cord is attached
to the margin of the placenta.
b. Velamentous attachment: The cord is attached to the amnion
away from the placenta.
49
4- Abnormalities regarding the position:
If the blastocyst implants in the lower segment of the uterus, the
placenta will develop in this segment close to the internal os. This
placenta is called the placenta previa. This case may lead to severe
bleeding during late pregnancy or during delivery, and the baby may
suffer from asphyxia during labor. The placenta previa may be one
of three types:
a. Placenta previa parietalis:
The placenta does not reach the internal os. It is the least
dangerous type.
b. Placenta previa marginalis:
The lower margin of the placenta reaches the internal os.
c. Placenta previa centralis:
The center of the placenta overlies the internal os. This is the
most dangerous type.
50
Fig. 28: Abnormalities of the placenta
FETAL MEMBRANES
AMNION

The amnion is the membrane which surrounds the amniotic cavity, and
is connected to the ectoderm at the amnio-ectodermal junction.
 Development:
- During the 8th day of development, a cavity called the amniotic
cavity appears within the epiblast. The epiblast cells adjacent to the
cytotrophoblast are called amnioblasts which form the roof of the
amniotic cavity, while its floor is formed of the rest of the epiblast
(Fig. 9).
- With formation of the extraembryonic mesoderm during the 11th and
12th days, the layer of amnioblasts becomes separated from the
cytotrophoblast, and is called now the amnion (Fig. 12).
- After gastrulation and the formation of the three germ layers during
the 3rd week, the amnion becomes attached to the ectoderm along the
margins of the disc (amnio-ectodermal junction).
- As a result of folding, the embryo is shifted inside the amniotic
cavity, and the amnio-ectodermal junction is shifted toward the
ventral side of the body in the form of a ring called the primitive
umbilical ring. With excessive shifting of the embryo inside the
amniotic cavity, the primitive umbilical ring is narrowed and
elongated to form the primitive umbilical cord (Fig. 20).
- With advance of pregnancy, the amniotic cavity increases in size so
that by the 3rd month the amnion comes in contact with the chorion
and they form together the amnio-chorionic membrane, thus the
chorionic cavity is obliterated (Fig. 24).
- With excessive enlargement of the amniotic cavity, the amniochorionic membrane (covered with the decidua capsularis) come in
contact with the decidua parietalis, thus the uterine cavity is
obliterated, and now the amniotic cavity occupies all the inside of the
uterus (Fig. 24).
 The amniotic fluid:
- It is a clear watery fluid secreted by the amniotic cells and fills the
amniotic cavity.
- Amount:
30 ml at 10 weeks.
300 ml at 20 weeks.
900 ml at 30 weeks.
1-1.5 liters at 37 weeks till full term.
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- Functions:
1- It absorbs external jolts.
2- It prevents adherence of the embryo to the amnion.
3- It acts as a heat insulator so protects the embryo against high
temperature if the mother is feverish.
4- It gives a space for movements of the embryo as these
movements are important for development of the muscles.
5- It gives a space for accumulation of urine and mechonium which
is a greenish fluid that passes out from the anal orifice of the
fetus.
6- From the beginning of the 5th month, the fetus swallows the
amniotic fluid. Most of the swallowed fluid is absorbed through
the gut of the fetus to its blood stream then to the maternal
circulation through the placenta. By this swallowing, the fetus
learns suckling, and the muscular wall of the gut and its digestive
glands develop properly.
7- During labor, the amniotic fluid has the following functions:
a- It protects the baby against the strong uterine contractions.
b- It helps to dilate the cervix of the uterus by formation of the
forebag of water which has a high hydrostatic pressure.
c- When the amnio-chorionic membrane ruptures, the sterile
amniotic fluid washes the vagina just before delivery.
- Abnormalities:
1- Polyhydramnios:
- It is the increased amount of the amniotic fluid in the last
weeks of pregnancy more than 2 liters.
- Causes:
a- Idiopathic in 35% of cases.
b- Maternal diabetes.
c- Congenital malformations including the central nervous
system as anencephaly.
d- Congenital malformations including gastrointestinal
atresias as esophageal atresia that prevent the infant from
swallowing the fluid.
2- Oligohydramnios:
- It is the decreased amount of the amniotic fluid in the last
weeks of pregnancy less than 1/2 liter.
- It is a rare condition that may result from renal agenesis.
3- Premature rupture of the amnion:
- It is usually of unknown cause.
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- It is the most common cause of preterm labor
UMBILICAL CORD
 Development
A. Primitive umbilical cord:
- During the 8th day of development, a cavity called the amniotic
cavity appears within the epiblast. The epiblast cells adjacent to
the cytotrophoblast are called amnioblasts which form the roof of
the amniotic cavity, while its floor is formed of the rest of the
epiblast..
- With formation of the extraembryonic mesoderm during the 11th
and 12th days, the layer of amnioblasts becomes separated from
the cytotrophoblast, and is called now the amnion.
- After gastrulation and the formation of the three germ layers
during the 3rd week, the amnion becomes attached to the ectoderm
along the margins of the disc (amnio-ectodermal junction).
- As a result of folding , the embryo is shifted inside the amniotic
cavity, and the amnio-ectodermal junction is shifted toward the
ventral side of the body in the form of a ring called the primitive
umbilical ring. With excessive shifting of the embryo inside the
amniotic cavity, the primitive umbilical ring is narrowed and
elongated to form the primitive umbilical cord. The primitive
umbilical cord. (Fig. 30) contains:
1- The connecting stalk.
2- The allantois and the allantoic vessels
3- The yolk sac and the yolk sac stalk accompanied by the
vitelline vessels.
4- Part of the extraembryonic coelom.
- During this stage, the abdominal cavity is temporarily too small
for the rapidly developing intestinal loops so some of them are
pushed outward into the extraembryonic coelom within the
primitive umbilical cord, this is called the physiological umbilical
hernia which normally occurs in the 6 th week of pregnancy. At
about the end of the 12th week, the intestinal loops are withdrawn
into the body of the embryo and the cavity in the cord is
obliterated.
53
Fig. 29: Primitive umbilical cord
54
B. Definitive umbilical cord:
- The mesoderm of the connecting stalk is transformed into a soft
jelly-like tissue called Wharton's jelly
- The extraembryonic part of the allantois disappears, while its
intraembryonic part (called urachus) is transformed into a
ligament called the median umbilical ligament that extends from
the apex of the urinary bladder to the umbilicus. The allantoic
blood vessels are enlarged and transformed into umbilical vessels
(two arteries and one vein).
- The yolk sac, yolk sac stalk and the accompanying vitelline
vessels disappear.
- The extraembryonic coelom gradually disappears by
approximation of the edges of the amnion.
Thus, the definitive umbilical cord becomes a tube of amnion
containing the umbilical vessels (two arteries and one vein)
embedded in the Wharton's jelly. It connects the ventral side of the
embryo to the placenta. The length of the full term cord is about 50
cm and it is tortuous to allow for fetal motility.
 Abnormalities
1- Very long or very short cord: The very long cord may be twisted
around the fetus and this may obstruct the circulation inside the cord.
The very short cord may be torn during the fetal movements.
2- Marginal or velamentous attachment of the cord.
3- Presence of one umbilical artery only. This leads usually to severe
congenital anomalies.
4- Omphalocele: It is an enlargement in the proximal part of the
umbilical cord containing intestinal loops. This case results from non
reduction of the physiological umbilical hernia.
5- Knots in the umbilical cord: The true knots obstruct the blood flow
and this leads to death of the fetus. However, the false knots of the
cord, which are swellings on its surface due to excessive tortuosity of
the umbilical vessels or local accumulation of Wharton's jelly, are
normal findings and carry no harm.
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YOLK SAC
 Development
1- Primary yolk sac:
During the 9th and 10th days of development (Fig. 12), a layer of flat
cells arise from the hypoblast and form a membrane called Heuser's
(exocoelomic) membrane which lines the inner surface of the
cytotrophoblast. The original blastocele is now called the 1ary yolk
sac (exocoelomic cavity) whose roof is the hypoblast and its floor is
Heuser's membrane.
2- Secondary yolk sac:
With enlargement of chorionic cavity during the 13 th and 14th days of
development (Fig. 12), the 1ary yolk sac is pinched off and thus
transformed into a smaller cavity called 2ary yolk sac. After
gastrulation during the 3rd week of development, the roof of the yolk
sac becomes formed of endoderm, while its floor is formed of
Heuser's membrane. After folding of the embryonic disc (Fig. 20),
the 2ry yolk sac forms the gut which is divided into fore-, mid- and
hindguts. A diverticulum called the allantois extends from the
hindgut into the umbilical cord. The rest of the yolk sac forms the
definitive yolk sac and the yolk sac stalk which are attached to the
mid gut. Small blood vessels called vitelline vessels appear on the
wall of the definitive yolk sac and the yolk sac stalk and are
connected to larger embryonic vessels. Later on the definitive yolk
sac, the yolk sac stalk and the extraembryonic parts of the vitelline
vessels are gradually reduced till disappear completely.
 Functions
1- Formation of the gut.
2- The primordial germ cells are formed in the wall of the yolk sac
close to the allantois.
3- The blood cells are originally formed by the mesoderm covering the
wall of the yolk sac.
4- The intraembryonic parts of the vitelline arteries form the celiac
trunk, superior and inferior mesenteric arteries, while the
intraembryonic parts of the vitelline veins form the portal vein, the
hepatic veins and the liver sinusoids.
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TWINS
.
 Dizygotic (Fraternal) twins:
- This is the most common type of twins. Approximately two-thirds of
twins are dizygotic, and their incidence is 7-11 per 1000 births. They
result from simultaneous shedding of two oocytes and their
fertilization by two different sperms.
- Both zygotes implant individually in the uterus and each develops its
own amnion, chorionic sac and placenta.
- Since both zygotes have a totally different genetic constitution, the
offsprings have no more resemblance than brothers or sisters of
different ages, and they may or may not have the same sex.
 Monozygotic (Identical) twins:
- Their incidence is 3-4 per 1000 births. They develop from a single
fertilized ovum but the resulting zygote splits into two. This splitting
may be at various stages of the early development of the zygote.
- Types
1- Very early separation of the morula:
The morula divides into two and each develops into a blastocyst.
Both blastocysts implant separately in the uterus and each develops
its own amnion, chorionic sac and placenta as the case of dizygotic
twins.
2- Separation of the inner cell mass of an early blastocyst :
The two embryos have a common placenta and a common
chorionic cavity, but each of them has its own amniotic cavity.
3- Separation of the bilaminar germ disc of a late blastocyst:
The two embryos have a common placenta, a common chorionic
cavity and a common amniotic cavity. Incomplete separation of the
bilaminar germ disc results in conjoined (Siamese) twins. Several
of such conjoined twins have been successfully separated by
surgical procedures.
- Since the monozygotic twins arise from one ovum and one sperm, they
are of the same sex and they are identical in their external features.
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2 cell-stage zygote
Blastocele
Amniotic cavity
Amniotic cavity
Yolk sac
Common chorionic cavity
Common placenta
Common amniotic cavity
Fig. 30: Types of twins
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Fig. 31: Monozygotic twins
 Twin defects:
1- A tendency toward prematurity. Approximately 12% of premature
infants are twins.
2- Low birth weight
3- A high incidence of perinatal mortality. About 10 to 20% of infants
die, compared with only 2% of the infants from single pregnancies.
The incidence of twinning may be much higher, since many twins
die before birth and some studies indicate that only 29% of women
pregnant with twins actually give birth to two infants. The term
vanishing twin refers to the death of one fetus .which occurs in the
first trimester or early second trimester and may result from
resorption or formation of fetus papyraceus in which one fetus is
large while the other is compressed and mummified.
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BIRTH DEFECTS
FACTORS REPONSIBLE FOR BIRTH DEFECTS
A- Environmental factors
Many environmental factors (teratogens) can cause birth defects as fetal
death, congenital malformations, growth retardation or functional
disorders. The effect of the teratogens varies according to:
1- The developmental stage at the time of exposure to the teratogens. The
most sensitive period for inducing birth defects is the 3rd to 8th weeks of
pregnancy which is the period of embryogenesis, however, defects may
also be induced before or after this period; no stage of development is
completely safe.
2- The dose and duration of exposure to the teratogens.
The environmental teratogens include:
Infectious agents
1- Viruses:
- The most dangerous viruses of a definite teratogenic effect are:
German measles, cytomegalovirus, herpes simplex, varicella and
human immunodeficiency virus (HIV).
- Other viruses that may have a teratogenic effect include: Measles,
mumps, influenza, hepatitis, poliomyelitis.
2- Bacteria as syphilis.
3- Parasites as toxoplasmosis.
A complicating factor introduced by the infectious agents is that most of
them lead to hyperthermia which is implicated by itself as a teratogen.
Radiations
Ionizing radiations (as X-ray, gamma ray) and atomic radiations have a
teratogenic effect because:
a- They kill the rapidly proliferating cells.
b- They lead to genetic alterations of the germ cells with subsequent
malformations.
Drugs and chemicals
- Most of the drugs have a teratogenic effect even the aspirin which is the
most commonly ingested drug during pregnancy may harm the
developing offspring when used in large doses. According to their
teratogenic effect, the drugs are classified into: drugs of a high
teratogenic effect, drugs of a mild teratogenic effect and safe drugs. It is
advised that the mother should avoid taking any drugs, even the
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considered safe drugs, during the first two months of pregnancy.
Examples of the highly teratogenic drugs are: Thalidomide, antiepileptic
drugs, antianxiety drugs, antidepressant drugs, vitamin A, synthetic
estrogens and many antibiotics as tetracyclines, chloramphenicol,
streptomycin and sulphonamides.
- Of the commonly ingested chemicals, alcohol and nicotine have a
definite teratogenic effect. Also, it was reported that many insecticides
and mercury-containing fungicides are teratogenic.
Maternal diabetes
The risk of congenital malformations in children of diabetic mothers is 3 or
4 times that in the offsprings of nondiabetic mothers and has been reported
to be as high as 80% in the offsprings of mothers with long-standing
diabetes.
B- Chromosomal and genetic factors
 Chromosomal abnormalities
The chromosomal abnormalities may be either numerical or structural.
1- Numerical chromosomal abnormalities
They originate usually due to non-disjunction of the homologus
chromosomes during anaphase of meiosis. This results into gametes
with either extra or less chromosomes. The non-disjunction may
affect either the autosomes or the sex chromosomes.
Autosomal abnormalities
1. Trisomy 21 (Down syndrome) (Mongolism):
- Each cell of the body of this individual contains an extra copy
of the chromosome 21, so the chromosomal number of the cell
is 47 (45+XX or 45+XY). It results usually from nondisjunction of homologus chromosomes 21 during the
formation of the oocycte resulting in an ovum of 24
chromosomes with an extra copy of the chromosome 21. The
incidence of Down syndrome is approximately 1 in 2000
pregnancies for women under age 25. This risk increases with
maternal age to 1 in 300 at age 35 and 1 in 100 at age 40.
- Individuals of Down syndrome suffer from:
a- Growth retardation.
b- Varying degrees of mental retardation.
c- Craniofacial abnormalities including upward slanting eyes,
epicanthal folds ( extra skin folds at the medial corners of
the eyes), flat facies and small ears.
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d- These individuals also have relatively high incidence of
cardiac defects, hypotonia, leukemia, infections, thyroid
dysfunctions and premature aging.
2. Trisomies 13, 15, 17, and 18 are less common than Trisomy 21.
The infants of these syndromes are mentally retarded with many
congenital malformations and usually die by the age of two
months.
Sex chromosomal abnormalities
1. Klinefelter syndrome:
- This syndrome, which is usually detected at puberty, affects
males where each cell of the body of this affected individual
contains an extra copy of the X chromosome, so the
chromosomal number of the cell is 47 (44+XXY). It results
usually from non-disjunction of the two X chromosomes
during the formation of the oocycte resulting in an ovum of 24
chromosomes with an extra copy of the X chromosome. When
this ovum is fertilized by a normal sperm containing Y
chromosome, the genotype of the offspring will be 44 + XXY.
The incidence of Klinefelter syndrome is approximately 1 in
500 males.
- Individuals of Klinefelter syndrome suffer from:
a- Sterility with testicular atrophy and usually gynecomastia..
b- There may be some degree of mental impairment.
2. Turner syndrome
- This syndrome affects females where each cell of the body of
this affected individual contains one X chromosome only, so
the chromosomal number of the cell is 45 (44+XO). It results
from non-disjunction of the sex chromosomes during
formation of either male or female gametes.
- Most of the
fetuses (98%) of Turner syndrome are
spontaneously aborted. The few that survive suffer from:
a- Sterility with ovarian atrophy.
b- Mental retardation.
c- Short stature, skeletal deformities and broad chest with
widely spaced nipples.
2- Structural chromosomal abnormalities
- The chromosomes are liable to breaks due to many environmental
factors as viruses, radiations and drugs. These breaks are rapidly
repaired, however, in some cases a broken piece of a chromosome
may be lost so the chromosome loses this piece (chromosomal
deletion).
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- Examples of chromosomal deletion:
a- Cri-du-chat syndrome: It is a well-known syndrome, caused
by partial deletion of the short arm of chromosome 5. Such
children have a catlike cry, microcephaly, mental retardation
and congenital heart disease.
b- Angelman syndrome: It results from deletion of a short
segment of the long arm of chromosome 15. Such children are
mentally retarded, cannot speak, exhibit poor motor
development, and are prone to unprovoked and prolonged
periods of laughter.
 Genetic abnormalities
- Single gene mutations are responsible for about 8% of all human
congenital malformations. If the mutant gene produces an
abnormality despite the presence of its normal allele, it is a dominant
mutation. On the other hand, if both alleles must be abnormal to
produce an abnormality, it is a recessive mutation.
- Some important metabolic diseases are caused by single gene
mutations for example phenylketonuria, homocystinuria and
galactosemia.
PRENATAL DIAGNOSIS
Several techniques are used for assessing the growth and development of
the fetus in utero and diagnosis of congenital malformations. These
techniques include:
1. Ultrasonography: It is a safe noninvasive technique that uses highfrequency sound waves reflected from tissues to create images. The
approach may be transabdominal or transvaginal. Some measurements
are used to assess the fetal growth as the crown-rump length, the
biparietal diameter of the skull, the length of the femur and the
abdominal circumference.
2. Maternal serum screening tests especially for alphafetoprotein (AFP)
concentration. AFP is produced normally by the fetal liver and leaks
into the maternal circulation. It can be detected in the maternal serum
during the second trimester (with a peak at 14 weeks) then begins to
decline after 30 weeks of gestation. Its level increases in certain
anomalies especially the neural tube defects and omphalocele. Its level
decreases in other conditions, as in Down syndrome, Trisomy 18 and
sex chromosomal abnormalities.
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3. Amniocentesis: A sample of the amniotic fluid is obtained by a needle
inserted transabdominally into the amniotic cavity. The technique is not
performed before 14 weeks when sufficient quantities of fluid are
available without endangering the fetus. Chromosomal studies of the
fetal cells sloughed into the amniotic fluid allow for diagnosis of
chromosomal and genetic diseases.
FETAL THERAPY
1. Fetal transfusion: It is used in cases of fetal anemia. Ultrasound is used
to guide insertion of a needle into the umbilical vein.
2. Fetal medical treatment: In many cases the treatment is provided to the
mother and reaches the fetus through the placenta. However, in some
cases, drugs may be administered to the fetus directly by intramuscular
injection into the gluteal region or via the umbilical vein.
3. Fetal surgery: Operating on fetuses has become possible. However,
because of the risks to the mother and the fetus, this type of surgery is
only performed in centers with well trained teams and when there are
no reasonable alternatives.
4. Stem cell transplantation and gene therapy: Because the fetus does not
develop any immunocompetence before 18 weeks of gestation, it may
be possible to transplant tissues or cells before this time without
rejection. Research in this field is focusing on the hematopoietic stem
cells for treatment of immunodeficiency and hematologic disorders.
Gene therapy for some inherited diseases is also being investigated.