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The gametes
Primordial germ cells appear in the yolk sac early in the
4th week of gestation then they migrate via the dorsal
mesentry of the hide gut to the gonadal ridges. During 6th week
they migrate to the underlying mesenchyme & become
incorporated in the primary sex cords
Determination of gonadal sex?
Spermatogenesis
With establishment of embrionic testis multiplication of germ cells ends& they
enter a long resting phase
At puberty, the germ cells (spermatogonia) increase in no. and after several
mitotic divisions , spermatogenesis is initiated
The total process of spermatogenesis from spermatogonium to mature sperm
takes 72 days.
Oogenesis
During early fetal life the oogonia proliferate by mitotic division then enlarg to
form the primary oocyte & ovarian stromal cells form a single layer of
flattened cells around it . This structure is called the primordial follicle
In the human female fetus of 20 weeks of gestation there are 7 million oocyte .
Those primary oocyte are arrested at the prophase of the first meiotic
division which is completed only after puberty just before ovulation
No primary oocyte is formed after birth , while there is continuous production of
spermatocyte after puberty
Menstrual cycle & ovulation
At time of puberty the female begins to undergo a regular monthly
cycles (menst. cycles) . The hypothalamus release GnRH that
stimulate the cells in anterior pituitary which in turn will secrete
the gonadotropin(LH & FSH) ,these hormones stimulate &
control the cyclical changes in the ovary.
At the beginning of each ovarian cycle a no. of primordial fpllicles
(5 to 12) ,begin to grow under the effect of FSH . Under normal
conditions only on of these follicles reaches full maturity & only
one oocyte is discharged , the others degenerate & become
atretic follicle which is replaced by fibrous tissue.
During the growth of the follicle , a large no. of cells will
surround the oocyte ,the inner cells called Granolosa cells that
secrete estrogen & the outer cells called theca interna &theca
externa cells
Estrogen will stimulate pituitary gland to secrete LH which is
needed for final follicular maturation & ovulation
Ovulation
In the days before ovulation the Graafian follicle increase rapidly
in size under the effect of FSH & LH to diameter of 16 mm.
In the meantime the surface of the ovary begins to bulge locally
& on the apex an avascular spot appears, the so called
stigma .
As a result of local weakening & degeneration of the ovarian
surface, follicular fluid oozes through the stigma which
gradually opens & subsequently the tension in the follicle is
released & the ovum together with surrounding cumulus
oophorus cells breaks free & float out of the ovary, this is called
ovulation
At the same time of ovulation the primary oocyte will resumes &
finishes its first meiotic division which result in the extrusion of first
polar body & secondary oocyte (ovum) that is arrested at the
metaphase of the second meiotic division that is only completed
at time of fertilization
Corpus luteum
Following ovulation the remaining follicular cells in the wall of the
ruptured follicle become vascularised by surrounding vessels &
under the effect of LH these cells develop a yellowish pigment
& change to luteal cells which form the corpus luteum
&secrete progesterone which induce secretory changes in the
endometrium in preparation for implantation of embryo.
Ovum transport
Shortly before ovulation , the fimbriae of the fallopian tubes begin
to cover the surface of the ovary & the tubes itself begin to
contract rhythmically.
The ovum surrounded by cumulus oophorous is carried into the
tube by the sweeping movement of the fimbriae & the motion of
the cilia of the lining epithelium
Once the oocyte is in the tube ,it is pushed toward the uterine
cavity by contraction of the muscular wall .
The fertilized ovum reaches to the uterine cavity in about 4
days.
If fertilization failed to occur , the corpus luteum reaches
maximum development about 9 days after ovulation & can
easily recognized as a yellowish projection on the surface of the
ovary. Subsequently it degenerate forming a mass of fibrous
tissue known as corpus albicans thus progesterone
production decreases thus precipitating menstrual bleeding.
If the ovum is fertilized , degeneration of corpus luteum is
prevented by a gonadotropic hormone secreted by the
trophoblast of the developing embryo (HCG) ,forming corpus
luteum of pregnancy that continue to secrete progesterone till 8
-10 weeks of pregnancy then the developing placenta takes
place of progesterone production.
Thus removal of corpus luteum before this period leads to
abortion
Fertilization
Fertilization is the process by which the male & female gametes
fuse, it occurs in the ampullary region of the tube which is the
widest portion of it. If the ovum is not fertilized it will die after 24
hrs.
the spermatozoa pass rapidly from the vagina to the uterus then
to the tubes & they should undergo changes to be capable of
fertilizing the ovum, those changes are:
1. Capacitating : it take place in the female genital tract
During this process a glycoprotien coat & seminal plasma
proteins are removed from the plasma membrane that
overlies the acrosomal region of the sperm . Completion of
capacitation permits the acrosome reaction to occur
2. Acrosome reaction : it occurs near the ovum ,
morphologically multiple points of fusion between the
plasma mem.& the outer acrosomal mem. take place ,
permitting the release of the acrosomal content that are
needed to penetrate the corona radiata & zona pellucida
During the acrosome reaction the following substances are
released
1.Hyaluronidase needed to penetrate the corona radiata barrier.
2.Trypsin – like substance needed for digestion of zona pellucida.
3.Zona lysin attached to the inner surface of the acrosomal mem.
also needed for penetration of zona pellucida.
AS soon as the sperm has entered the ovum ,the later respond
in three different ways :
1.Cortical & zona reaction that the zona pellucida & plasma mem.
Become impenetrable to other sperm to prevent polyspermia.
2. Resumption of the second meiotic division resulting in send
polar body & a large definitive oocyte forming the female
pronucleus.
3. Metabolic activation of the egg
After the sperm has entered the oocyte it move forward
until it lies in close proximity to the female pronucleus.
Its nucleus swollen forming male pronucleus. The tail
is detached & degenerate. The main result of
fertilization are:
1.Restoration of the diploid no. of chromosomes, thus
the zygote have 46 chromosomes ,23 of paternal &
23 of maternal origin.
2.Determination of the sex of the new individual.
3.Initiation of cleavage. Without fertilization the oocyte
usually degenerate 24 hrs after ovulation.
Cleavage & blastocyst formation
Once the zygot has reached the tow – cell stage ,it undergoes a
series of mitotic divisions, resulting in a rapid increase in no. of
cells. These cells , which become smaller with each cleavage
division, are known as blastomeres
After three or four divisions the zygot, similar in appearance to
a mulberry, is known as morula.
This stage is reached about three to four days after fertilization
& the embryo is about to enter the uterus .At this time (16 cell
stage) the morula consist of a group of centrally located cells
,the inner cell mass that give rise to the tissues of the embryo
proper, and surrounding layer ,the outer cell mass that forms
the trophoblast which later on contributes to the placenta
At about the time that the morula enters the uterine cavity , fluid
begins to penetrate through the zona pellucida into the
intercellular space of the inner cell mass .Gradually the
intercellular space become confluent and finally a single cavity,
the blastocele ,is formed at this time the embryo is known as
blastocyst .
The cells of the inner cell mass, now referred to as embryoblast,
are located at one pole, while those of the outer cell mass, or
trophoblast, flatten &form the epithelial wall of the blastocyst.
The zona pellucida now disappear, allowing implantation to
begin.
The trophoblastic cells over the embryublast pole begin to
penetrate between the epithelial cells of the uterine mucosa at
about 6th day. This penetration & subsequent erosion of the
epithelial cells of endometerium result from proteolytic enzymes
produced by the trophpblast
Implantation
Following ovulation , the corpus luteum grows near the surface
of the ovary as it produces progesterone . Under this hormonal
influence , the endometrium & its glands undergoes rapid
morphological changes leading them to secretory phase .
Other factors than gonadal steroid influence uterine receptivity
for implantation which are local peptides such as growth factors
including epidermal growth factor( EGF) , insulin – like growth
factor -1 (IGF -1) & its binding protein (IGFBP -1) , plasminogen
activator
By the sixth day ,the zygote orient itself towards the decidua &
begin to penetrate its epithelia surface by piercing the
basement mem. at the embryonic pole
Once inside the decidua it generate extracellur matrix (ECM)
which is thought to enhance the chance of implantation . This
process facilitate one of earliest embryo – maternalinteraction
such as secretion of HCG by the trophoblastic cells leading to
maternal recognition of pregnancy.
Endometrial cytokines modulate cytotrophoblastic proteolytic activity to
control the depth of invasion.
By the 8th day of developm. embryo is partially embedded in the decidua . The
trophoblast at the area over the embryoblast differentiate into 2 layers
1.An inner layer of mononuclaeted cells , the cytotrophpblast.
2.An outer layer of multinucleated zone without distinct cell
boundaries, the cynsytiotrophpblast or cynsytium.
The cells of embryoblast also differentiate into 2 layers
1.A layer of small cuboidal cells, the endodermal germ layer.
2.A layer of columnar cells, the ectodermal germ layer.
At the same time a small cavity appear within the ectoderm & enlarge to form
the amniotic cavity. Those ectodermal cells adjacent to the cytotrophoblast
are called amnioblast, & together with the rest of ectoderm they line the
amniotic cavity.
There is hypereamia & oedema at & adjacent to the implantation site that can
be seen as 1mm red spot on the mucosa at about 11-12 days due to
maternal blood in lacunar space .
Day 8
D
By day 9 lacunae develop in the syncytiotrophoblast & when
maternal sinusoids are eroded by the syncytium , maternal
blood enters the lacunar network & by the end of the second
week a primitive uteroplacental circulation begins .
The penetration defect in the surface epithelium is closed by
fibrinous material.
The cytotrophpblast , meanwhile, forms cellular columns
penetrating into & surrounded by the syncytium. These
columns are the primary stem villi. By the end of the second
week the blastocyst is completely embedded & the surface
defect in the mucosa has healed.
day 9
day 12
Day 13
Embryonic period
It is the period following fertilization that the re is differentiation
of cells into specialized tissues, to form inter-related organ
systems. It start with the generation of the embryonic disk
during 2nd week post fertilization & ends by the last day of the
8th week (10 week after the last menstrual period) . At this point
all organ systems are formed ,but not necessarily mature or
functioning.
3rd week
On the dorsal aspect of the bilaminar germ disk a faint groove,
the primitive streak, appears on the midline near its caudal end
& it will determines symmetry & defines the cephalic & caudal
poles of the embryo.
During 3rd week, tow other structures become apparent on
embryonic disc , the neural plate & the somites which appear
as symmetric eminencies
Internally , the bilaminar embryo generates the mesodermal
layer made up of cells which forms the primitive node , at the
cephalic end of primitive streak,& migrate between endodermal
& ectodermal layers
The somites composed of paraxial mesodermal cells will
appear at day 20, at a level corresponding to the future base of
skull.
the primery yolk sac (extra embryonic structure) also grow
rapidly during this period & is necessary for exchanging
metabolites bet. Mother & embryo at that time when there is no
placenta It will degenerate by the end of 6th week
The amniotic mem. Is another extra embryonic structure that
develops during this period.
4th week
During this week the embrionic disc folds into an embrionic
cylinder within which is a cranio – caudal blind-ending tube
which has 3 segments , the foregut , the mid-gut opened to the
developing yolk sac & the hindgut. This stage marks the start of
organogenesis.
The 1st organ to become apparent is the primitive heart in the
form of a forward buckling loop. cardiac activity is evident by
day 22 post fertilization.
Development of nervous system , takes place at this stage& by
the end of 4th week the central nervous system has defined
segments.
Toward the end of 4th week , the foregut septates along the
midline into the respiratory &digestive primitive elements. Also
the mesonephric duct & the mesonephros will
In summary ,by the end of the 4th week the ,almost all organ
systems ,till immature , can be identified
Toward the end of 4th week the body of embryo is attached to
the yolk sac by a broad viteline duct & two connecting viteline
blood vessels .The yolk sac is placed within the exocoelomic
space. The viteline duct & vessels are included within the
umbilical cord just before the cord enters into the amniotic sac.
In the cephalic pole of the embryo , five pharyngeal arches
appear in succession .
Further development of trophoblast
By the beginning of the 3rd week the trophoblast is
characterized by primary stem villus which consist of a
cytotrophoblastic core covered by a syncytial layer.
During further development ,mesodermal cells penetrate the
core of primary villi & grow in of decidua, this newly formed
structure is called the secondary stem villus .
By the end of the 3rd week the mesodermal cells in the core of
the villus begin to differentiate into blood cells & small blood
vessels, thus forming the villous capillary system. The villus
now is known as tertiary stem villus .
The capillaries in the tertiary villi make contact with capillaries
developing in the mesoderm of the chorionic plate & in the
connecting stalk. These in turn establish contact with the intraembryonic circulatory system , thus connecting the placenta &
embryo
Hence ,when the heart start to beat in the 4th week of
development, the villous system is ready to supply the embryo
with the necessary nutrient & oxygen.
Meanwhile, the cytotrophoblastic cells in the villi penetrate into
the overlying syncytium until they reach the maternal decidua.
Here they establish contact with similar extension of
neighboring villous stem, thus forming a thin outer
cytotrophoblastic shell.
By the 20th day the embryo is attached to its trophoblastic
shell by a narrow connecting stalk. The connecting stalk
later develops into the umbilical cord which forms the
connection between the placenta & the embryo.
From time of their formation in the 3rd week till the end of 1st
trimester , the villi are covered by a single layer of
cytotrophoblast & an outer layer of syncytium which is in
immediate contact with maternal blood in the intervillous space.
After 20 weeks the cytotrophoblast begin to disappear & finally
only a thin layer of capillary endothelium & syncytial membrane
which separate between fetal & maternal blood.
Further development of the placenta
The chorionic villi are formed in huge no. & constitute the
bulk of the placental area.
At first the villi are formed allover the surface of gestational.
As growth proceed, the decidua capsularis becomes thinner
& between 12 & 16 weeks , the villi on the decidua
capsularis degenerate rapidly leaving this side of the
chorion smooth (chorion leave)
In compensation, the villi on the surface opposed to the dicidua
basalis undergoes a great deal of hypertrophy (chorion
frondosum) & become matted into a solid disc which the fully
developed placenta which is formed by the 10th week.
Placenta at term
The placenta at term is cicular forming a spongy disc 20 cm. in
diameter & 3cm. In thickness 7 its weight is about 500 gm. But
there is direct relation with fetal weight.
The placenta has a fetal & maternal surface .
The fetal surface is covered smooth amnion underneath the
chorion.
The maternal surface is rough & spongy & presents a number of
polygonal areas known as cotyledons which are seperated
by shallow grooves
There are about 15 – 20 cotyledon & each one is corresponding to
a main villous system of branched villi.
The placenta is dull red in color & grey spots are frequently
seen on maternal surface which are the result of deposition of
calcium in the degenerated area & are more frequent after
term.
The chorion spread away from the edge of the placenta to form
the outer layer of fetal membranes which enclose the fetus &
amniotic fluid. The chorion & placenta are of the same origin.
The amnion which is a thinner layer underneath the chorion & can
be separated from chorion after birth.
The umblical cord usually reaches the fetal surface of placenta
at the midline of its disc but sometimes at its edge.
Blood coming to placenta from fetus through 2 umbilical arteries
& drained into a single umbilical vein
Functions of placenta
1.It act as fetal lung by continuous exchange of o2 &co2
2.Transport of nutrient material so it act as GIT during intrauterine
life.
3.Excreation of waste material & H ion, so it replace the function
of the kidney.
4.It play a role in the immune system of the fetus by transporting
Ig from maternal circulation & also it act as a barrier against
transport of some infections to the fetus.
5.It replace the function of the liver by detoxification of drugs &
chemical materials that are present in the maternal
circulation.
6.It has an endocrine function by secretion of some hormones as
estrogen, progesterone, HCG, lactogen, relaxin. These
hormones are secreted into the maternal circulation.
The estrogen secretion increase gradually during pregnancy &
reach its peak level gust before labour & it is mainly estriol.
The placenta synthesize estriol from androgenic precursor which
come from fetal adrenal.
Progesterone secretion is from corpus luteum till about 10
weeks , then the placenta becomes responsible for its secretion
& reaches its peak level just before labour .
Regarding HCG ,the β subunit can be detected in maternal
serum as early as 9 days after fertilization & in urine after 13
days from fertikization
It reaches its peak level in serum & urine at 8 – 10 weeks &
decreases thereafter.
It disappear from urine 7 days after termination of pregnancy.
Placental transport
The trophoblast & the underlying endothelium of fetal vessels
behave as semipermable membrane ,allowing the free passage
of water & soluble substances of relatively low molecular weight
(less than 1000) according to the law of osmotic equilibrium.
But there are other mechanism for transport across the placenta:
1.Simple diffusion : passage of the substance from area of high
concentration to area of low conc. According to chemical or
electrochemical gradient as oxygen.
2.Facilitated diffusion: transport is facilitated by a carrier molecule
& it does not require energy as transport of glucose.
3.Activ transport: requires a carrier molecule & energy because it
occur against chemical gradient as iron , amino acids.
4.Bulk transport: in this mechanism , water & small dissolved
molecules cross the membrane more quickly than by simple
diffusion.
5.Pinocytosis: the substance is enveloped by the cell membrane
to form a vesicle which is transported across thr placental
membrane.
6.Villous damage: a small break in the villous surface can allow
the passage of fetal blood cells into maternal circulation.
By this mechanism some bacteria, protozoa &T.Pallidum cross
the placenta
Efficient placental transport will depend on :
1.Maternal blood flow through the intervillous space.
This will depend on blood flow rate through uterine artery & spiral
arteriols (at term 8oo ml/min).
It is also affected by uterine contraction spatially during late
pregnancy & labour.
2.The effective surface area of the chorionic villi.
3. The fetal blood flow through the chorionic villi (about 300 ml/min
through the fetal capillaries.
The umbilical cord
The umbilical cord is the major connection between the fetus &
the placenta. It is derived from the ventral stalk.
The umbilical cord compose of :
1.Covering epithelium which is the amnion.
2.Wharton’s jelly which originate from extra-embryonic mesoderm
& consist of cells elongated processes in a gelatinous fluid.
3.Blood vessels : at first they are 4 in number ,2 arteries & 2
veins , after 12 weeks the veins unites to form a single umbilical
vein which carries oxygenated blood from placenta to the fetus .
The umbilical arteries originated from internal iliac (hypogastric
arteries) of the fetus & carry reduced blood from fetus to the
placenta.
4.Umbilical vesicle & its duct which is the remnant of the yolk sac
may be found as a small yellow body near attachment of the
cord to the placenta.
5.The allantois which occasionally found as a blind tube just
reaching into the cord & it is continuous inside the fetus with
the urachus & bladder.
The cord length is about 50 cm. & about 1 cm thickness , but it
is not uniform in thickness due to the presence of nodes &
swelling. These are called false knots ,they are caused by
local dilatation of umbilical vein or mostly due to localized
increase in Wharton’s jelly.
The cord may show a true knots due to the passage of the
fetus through a loop in the cord & these may cause impairment
of feto-placental circulation.
The cord may be coiled around fetal body , limbs or neck but
this does not cause serious problem unless it is coiled around
the neck more than 1 time then tension on the cord during the
2nd stage of labour with the descend of the fetus & this tension
may obstruct the feto-placental circulation & lead to fetal
distress