Cleavage, Blastocyst formation

and Implantation
By
Dr. A.U. Agu
MB,BS; MSc; PhD
 Cleavage
• Is the process of
subdivision of zygote into
smaller cells.
• Once the zygote reached 2
cell stage (30hrs after
ferti), it undergoes a series
of mitotic division
increasing the number of
cells.
• The cells become smaller
with each division & form
the blastomere
• The blastomeres are seen as
loosely arranged clump of cells
until eight-cell stage.
• Thereafter, the blastomeres
maximize their contact with
each other forming a compact
ball of cells held by tight
junction.
• This process of compaction,
segregates inner cells from
outer cells
• At about 3 days after
fertilization, the compacted
cells divide again to form 16-
cell morula (mulberry)
• Inner cells constitute the inner cell mass (ICM)
which gives rise to embryo proper
• The surrounding cells (outer cells), composed
the outer cell mass (OCM) & gives rise to
trophoblast which later contribute to
placenta.
NOTE.
 4-cell stage is formed at about 40hrs after ferti
 12-16 cell stage - at about 3 days
 Late morula – 4 days
 Blastocyst formation
• About the time the morula enters
the uterine tube, some fluid enter
into the intercellular space of inner
cell mass via the zona pellucida.
• As the fluid increases, the ICM
becomes separated from the OCM
and appears at one pole.
• A single cavity or cyst is formed
called blastocele.
• The embryo is thus called
blastocyst, ICM and OCM become
embryoblast and Trophoblast
respectively
• A single cavity or cyst is formed
(blastocele).
• The embryo is thus called
blastocyst, ICM and OCM become
embryoblast and trophoblast
respectively
• The trophoblast flatten & form
epithelial wall of the blastocyst
• Then zona pellucida disappears to
allow implantation
• The side of attachment of
embryoblast is called embryonic
pole while the opposite side is
abembryonic pole
 Function of zona pellucida
• The trophoblast has the property of being able
to stick into tissues & its cell can ‘eat up’ other
cells
• Thus they can invade & burrow into tissue
they come in contact
• Zona pellucida prevents the embryo from
sticking to the uterine tube
 Uterus at time of implantation
• The mucosa of the uterus is in secretive phase
• The uterine glands and arteries are coiled & the tissues
are succulent
• Thus 3 distinct layers of are recognized in the
endometrium;
 Superficial compact layer
 Intermediate sponge layer
 Thin basal layer
 Normally, implantation occur along the anterior of
posterior wall of the body of uterus.
 Implantation

• The trophoblastic cells

over the embryonic pole
begin to penetrate b/w
the epithelial cells of the
uterine mucosa
• Attachment and inversion
of trophoblast involves;
 Integrins – expressed by
trophoblast
 Laminin - extracellular
matrix molecule(EMM)
 Fibronectin - EMM
• Integrin receptors for laminin promote
attachment
• Those of fibronectin stimulate migration
• These molecules also regulate trophoblast
differentiation.
 Day 8

• Blastocyst is partially
embedded in the endometrial
stroma
• In the area over the
embryoblast, the trophoblast
differentiated into 2 layers;
 Cytotrophoblast – has mitotic
figures
 Syncytiotrophoblast
• Thus, cells of cytotrophoblast
divide & migrate into
syncytiotrophoblast where
they fuse & loose their
individual cell membranes
• The embryoblast also differentiates
into 2 layers:
 Hypoblast
 Epiblast
• Within the epiblast, a small cavity
appears & this enlarges to form the
amniotic cavity
• Epiblast cells line the amniotic
cavity.
• Those adjacent to cytotrophoblast
are called amnioblast
• Endometrial stroma adjacent to
implantation site becomes
edematous & highly vascular
• The tortuous glands secrete
glycogen & mucus
 Day 9
• Blastocyst is more deeply
embedded
• The penetration defect in
the surface epithelium is
closed by fibrin coagulum
• Trophoblast dev further
with vacuoles appearing
in the syncytiotrophoblast
• The vacuoles fuse to form
large lacunae & this stage
is called lacunar stage
• At the abembryonic
pole, flattened cells from
hypoblast forms
exocoelomic (Heuser’s)
membrane that lines the
inner surface of
cytotrophoblast
• The hypoplast & the
membrane form the
lining of primitive yolk
sac (exocoelomic cavity)
 Days 11 and 12

• Blastocyst is completely
embedded in the
endometrium
• Surface epith almost
entirely covers the
defect in the uterine wall
• The blastocyst produces
a slight protrusion into
the uterine lumen
• The lacunar spaces form
an intercommunicating
network
• The syncytiotrophoblast
penetrate deeper into the
stroma & erode the endothelial
lining of maternal capillaries
(sinusoids)
• The lacunae become continuous
with the sinusoid & maternal
blood enters the lacunar system
• Trophoblast erodes more
sinusoids, & maternal blood
flows via the trophoblast
system, establishing
uteroplacental circulation
• New cell populations
(extraembryonic mesoderm)
appear b/w the inner surface
of cytotrophoblast & outer
surface of primary yolk sac.
• They are derived from
primary yolk sac.
• Large cavities develop in the
extraembryonic mesoderm
• The cavities form spaces
called chorion cavity or
extraembryonic coelom
• The extraembryonic
mesoderm lining the
cytotrophoblast & amion is
called extraembryonic
somatopleuric mesoderm
• Those covering the primary
yolk sac is called
extraembryonic
splanchnopleuric mesoderm
• Decidua reaction first occur
at site of implantation but
soon occur throughout the
endometrium
 Day 13

• The surface defect of the

endometrium is healed
• Sometimes, bleeding occur
at the implantation site due
to increased blood flow to
the lacunar spaces
• Trophoblast is characterized
by villous structures
• Hypoblast proliferate & form
a new cavity within the
primary yolk sac & is called
secondary or definitive yolk
sac
• During its formation, a
portion of primary yolk
sac (exocoelomic cavity)
is pinched off & is called
exocoelomic cyst
• Extraembryonic coelom
expand & form a large
cavity called chorionic
cavity
• With dev of blood
vessels, connecting stalk
becomes the umbilical
cord
 Clinical correlates

• Synsytiotrophoblast
produces h C G, thus PT
can be positive by end of
2nd week
• Abnormal implantation
– At internal os giving
placenta previa
– Ectopic gestation
• Abnormal blastocyst
causing abortion of
hydatidform mole
Thanks for listening