‫الرحيم‬ ‫الرحمن‬ ‫هللا‬ ‫بسم‬
The First week After
Fertilization
Dr.Iqra Osman Abdullahi
 Cleavage consists of repeated mitotic divisions of the
zygote, resulting in a rapid increase in the number of
cells
[Moore et al, 2016]
 At this stage, each cell is called a blastomere
 Occurs as the zygote passes along the uterine tube
towards the uterus
 Zygote is still within the zona pellucida
 Approximately 3 days after fertilization, cells of the
compacted embryo divide again to form a 16-cell morula
(mulberry).
CLEAVAGE
 The zygote undergoes repeated division, passing through
these stages:
 2-cell stage
 4-cell stage
 8-cell stage
 16-cell stage
 When there are 16 or more blastomeres, the zygote is
considered a morula (a hollow ball of cells)
MORULA
 After the zygote formation, typical mitotic division of the
nucleus occurs by producing two blastomeres.
 The two cell stage is reached approximately 30 hours
after fertilization. Each contains equal cytoplasmic
volume and chromosome numbers.
 The blastomeres continue to divide by binary division
through 4, 8, 16 cell stage until a cluster of cells is formed
and is called morula, resembling a mulberry.
 As the total volume of the cell mass is not increased and
the zona pellucida remains intact, the morula
 after spending about 3 days in the uterine tube enters
the uterine cavity through the narrow uterine ostium (1
mm) on the 4th day in the 16-64 cell stage.
 The transport is a slow process and is controlled by
muscular contraction and movement of the cilia. The
central cell of the morula is known as inner cell mass
which forms the embryo proper and the peripheral cells
are called outer cell mass which will form protective
and nutritive membranes of the embryo.
BLASTULATION
 ● Compaction
 o The blastomeres change shape and tightly align
themselves against each other to form a compact ball
of cells
• Blastulation
 The process wherein the morula is transformed into
a blastula/blastocyst
• A group of cells compact around the
edge/periphery will form the outer cell
mass
• Another group of cells group together on one
side  will form the inner cell mass
 A blastula/blastocyst is a ball of cells with an outer cell
Blastocyst formation
 4 days post-fertilization, a fluid-
filled space appears-called
blastocystic cavity.
 fluid passes from uterus through
zona pellucida to the cavity.
 as fluid in cavity increases,
blastomeres separate into 2 parts
 thin, outer cell layer =
trophoblast
 inner cell mass = embryoblast
 the conceptus is now called a
blastocyst.
 blastocysts floats in uterine cavity
for about 2 days
 zona pellucida degenerates,
 As the cells become more functional, they differentiate
 Outer cell mass  Trophoblast
 Inner cell mass  Embryoblast
 The trophoblast differentiates into two specialized
layers that are important for the placenta:
 Cytotrophoblast
 Syncytiotrophoblast
 The embryoblast will differentiate into a
bilaminar disk, which is made up of:
 Epiblast
 Hypoblast
Figure 2. Cleavage and
Blastulation [Moore et al, 2016]
 Fig. 2.4:A to D schematic representation of
mitotic division f the zygote resulting formation of:
(A) Two cell stage (b) Four cell stage (C) Murula;
(D) Blastocyst.
Morula formation
QUICK OVERVIEW
After Fertilization:
The anterior pituitary releases LH to trigger the
ovulation process.
o Secondary oocyte is formed
o It is frozen in metaphase II.
o In the ampulla, fertilization occurs
o Cleavage process occurs, the cell transforms:
Oocyte → Zygote → 4-cell stage → 8-cell stage
→ 16-cell stage → Blastocyst
As these processes are occurring, the cells are
moving to
the uterine cavity at the same time.
Proteins in the blastocyst allow it to hook up onto
Figure 1. Fertilization and Ovulation
Structure of Trophoblast:
Structure of Trophoblast:
The outer cell is the trophoblast, it will
become:
o Cytotrophoblast
o Syncytiotrophoblast
The inner cell mass differentiated and
became more specialized to form the
bilaminar disc
Trophoblast forms:
o Part of chorion
o Part of placenta
This helps in providing oxygen and nutrients
and get rid of waste.
Figure 2. Cleavage of Cells After Fertilization
 Implantation occurs in the endometrium of the anterior or
posterior wall of the body near the fundus on the 6th day
which corresponds to the 20th day of a regular menstrual
cycle.
 Implantation occurs through four stages e.g. apposition,
adhesion, penetration and invasion.
 CHANGES IN THE BLASTOCYST: The polar trophoblast cells
adjacent to the inner cell mass are primarily involved in
adhesion to the endometrial cells.
 The factors responsible for blastocyst attachment are:
• P. selectin, heparin sulfate, proteoglycan, EGF, integrins,
trophinin and others. The signals for trophoblast multiplication
arise from the inner cell mass.
IMPLANATATION OF THE BLASTOCYST
continue
 ENDOMETRIUM AT THE IMPLANTATION SITE :
(1) The endometrium is in the secretory phase corresponding
to 20–21 days of cycle.
(2) The microvilli on the surface of the Trophectoderm
interdigitate with the decidual cells to form the junctional
complexes. Endometrial receptivity and molecular signaling
during implantation is induced by progesterone, LIF (leukemia
inhibitory factor), prostaglandins and COX-2.
Four Stages of Implantation:
1.APPOSITION :
 Occurs through pinopod formation. Pinopods are long
finger like projections (microvilli) from the endometrial
cell surface.
 These pinopods absorb the endometrial fluid which is
secreted by the endometrial gland cells. This fluid, rich
in glycogen and mucin provides nutrition to the
blastocyst initially. Unless this fluid is
absorbed,adhesion phase cannot occur.
2.Adhesion of blastocyst to the endometrium occurs
through the adhesion molecules like integrin, selectin and
cadherin (glycoproteins).
3.PENETRATION:
• Actual penetration and invasion occur through
the stromal cells in between the glands and is
facilitated by the histolytic action of the
blastocyst. With increasing lysis of the stromal
cells, the blastocyst is burrowed more and
more inside the stratum compactum of the
decidua (Fig. 2.5).
Fig. 2.5: schematic representation showing initial
implantation of the blastocyst in the stratum of
compactum of the decidua
Vacuoles appear in the advancing syncytium which fuse to form
large lacunae. These are more evident at the embryonic pole.
Concurrently, the syncytial cells penetrate deeper into the
stroma and erode the endothelium of the maternal capillaries.
The syncytium by penetrating the vessels, not only becomes
continuous with the endothelial lining but permits the maternal
blood to enter into the lacunar system. Ultimately erosion of few
maternal arteries with formation of blood space (lacunae)
occurs. Nutrition is now obtained by aerobic metabolic pathway
from the maternal blood. Further penetration is stopped
probably by the maternal immunological factor and the
original point of entry is sealed by fibrin clot and later by
epithelium. The process is completed by 10th or 11th day
which corresponds to D 24-25 from LMP (Fig. 2.5).
This type of deeper penetration of the human blastocyst is
called interstitial implantation and the blastocyst is covered
on all sides by the endometrium (decidua). Occasionally, there
may be increased blood flow into the lacunar spaces at the a
embryonic pole. This results in disruption of the lacunae and
extravasation of blood into the endometrial cavity. This
corresponds approximately to 13th day after fertilization
(at about the expected day of the following period). This
may produce confusion in determination of the expected
date of delivery. The process of implantation is controlled by
the immunomodulatory role of various cytokines (interleukins 3,
4, 5, 6, 10, 13), many local peptides like epidermal growth
factor (EGF), insulin like growth factor (IGF) and
prostaglandins. Both the decidua and the embryo synthesize
these molecules.
IMPLANATATION OF THE BLASTOCYST
• When the cell is implanted in the endometrium, cells
start proliferating outside the zona pellucida
• The cell membrane will disintegrate.
• It forms a fluid-like cytoplasm which consists of the
nuclei of the cell. Therefore, the cells lose their well-
defined margins
• Components of the cell will be released and all of the
cytoplasm will fuse together to form a syncytium
• This is called the syncytiotrophoblast
• At the base of the finger-like structures of the
syncytiotrophoblast there are well-defined margins.
• This is called the cytotrophoblast
• Syncytiotrophoblast will continue to release hydrolytic
enzymes to make its way through the uterine lining.
• The uterine lining has maternal blood vessels and the
syncytiotrophoblast will move deeper into the endometrium
until it becomes confluent with the maternal blood vessels
o Now the embryo can receive oxygen, nutrients,
hormones, etc.
• At day 24, the syncytiotrophoblast starts making β-hCG
• It stimulates the corpus luteum to continue producing
progesterone
o This helps avoid the endometrial lining from shedding
like in the normal cell cycles.
Figure 3. Implantation of the
Cell in the Uterus, showing the
structure of Trophoblast
BILAMINAR DISC
 This is the inner cell mass of the differentiated
blastocyst.
 It contains 2 sheet like layers (the top and bottom
layer)
(1) Top layer
Called the Epiblast
 o Above the epiblast is the amniotic cavity.
(2) Bottom layer
 Called the Hypoblast
 o Below the hypoblast is the yolk sac.
Figure 4. Bilaminar Disc Showing
Epiblast and Hypoblast
(3) From the top view
• On one end of the bilaminar disc (from the top view),
there is a depression → prochordal plate
o This is an area where the epiblast and hypoblast are
fused together.
o The prochordal plate helps to give orientation.
 As it is located in the cranial side, opposite to the
prochordal plate is the caudal side.
• On the caudal side, there is a membrane called the cloacal
membrane
o Becomes the anus
• On the cranial side, there is buccopharyngeal membrane
o Becomes the mouth
Figure 5. Bilaminar Disc from the top view
First week of development after fertilization.pptx

First week of development after fertilization.pptx

  • 1.
    ‫الرحيم‬ ‫الرحمن‬ ‫هللا‬‫بسم‬ The First week After Fertilization Dr.Iqra Osman Abdullahi
  • 2.
     Cleavage consistsof repeated mitotic divisions of the zygote, resulting in a rapid increase in the number of cells [Moore et al, 2016]  At this stage, each cell is called a blastomere  Occurs as the zygote passes along the uterine tube towards the uterus  Zygote is still within the zona pellucida  Approximately 3 days after fertilization, cells of the compacted embryo divide again to form a 16-cell morula (mulberry). CLEAVAGE
  • 3.
     The zygoteundergoes repeated division, passing through these stages:  2-cell stage  4-cell stage  8-cell stage  16-cell stage  When there are 16 or more blastomeres, the zygote is considered a morula (a hollow ball of cells)
  • 4.
    MORULA  After thezygote formation, typical mitotic division of the nucleus occurs by producing two blastomeres.  The two cell stage is reached approximately 30 hours after fertilization. Each contains equal cytoplasmic volume and chromosome numbers.  The blastomeres continue to divide by binary division through 4, 8, 16 cell stage until a cluster of cells is formed and is called morula, resembling a mulberry.  As the total volume of the cell mass is not increased and the zona pellucida remains intact, the morula  after spending about 3 days in the uterine tube enters the uterine cavity through the narrow uterine ostium (1 mm) on the 4th day in the 16-64 cell stage.
  • 5.
     The transportis a slow process and is controlled by muscular contraction and movement of the cilia. The central cell of the morula is known as inner cell mass which forms the embryo proper and the peripheral cells are called outer cell mass which will form protective and nutritive membranes of the embryo.
  • 6.
    BLASTULATION  ● Compaction o The blastomeres change shape and tightly align themselves against each other to form a compact ball of cells • Blastulation  The process wherein the morula is transformed into a blastula/blastocyst • A group of cells compact around the edge/periphery will form the outer cell mass • Another group of cells group together on one side  will form the inner cell mass  A blastula/blastocyst is a ball of cells with an outer cell
  • 7.
    Blastocyst formation  4days post-fertilization, a fluid- filled space appears-called blastocystic cavity.  fluid passes from uterus through zona pellucida to the cavity.  as fluid in cavity increases, blastomeres separate into 2 parts  thin, outer cell layer = trophoblast  inner cell mass = embryoblast  the conceptus is now called a blastocyst.  blastocysts floats in uterine cavity for about 2 days  zona pellucida degenerates,
  • 8.
     As thecells become more functional, they differentiate  Outer cell mass  Trophoblast  Inner cell mass  Embryoblast  The trophoblast differentiates into two specialized layers that are important for the placenta:  Cytotrophoblast  Syncytiotrophoblast
  • 9.
     The embryoblastwill differentiate into a bilaminar disk, which is made up of:  Epiblast  Hypoblast
  • 10.
    Figure 2. Cleavageand Blastulation [Moore et al, 2016]
  • 11.
     Fig. 2.4:Ato D schematic representation of mitotic division f the zygote resulting formation of: (A) Two cell stage (b) Four cell stage (C) Murula; (D) Blastocyst.
  • 12.
  • 13.
    QUICK OVERVIEW After Fertilization: Theanterior pituitary releases LH to trigger the ovulation process. o Secondary oocyte is formed o It is frozen in metaphase II. o In the ampulla, fertilization occurs o Cleavage process occurs, the cell transforms: Oocyte → Zygote → 4-cell stage → 8-cell stage → 16-cell stage → Blastocyst As these processes are occurring, the cells are moving to the uterine cavity at the same time. Proteins in the blastocyst allow it to hook up onto
  • 14.
  • 15.
    Structure of Trophoblast: Structureof Trophoblast: The outer cell is the trophoblast, it will become: o Cytotrophoblast o Syncytiotrophoblast The inner cell mass differentiated and became more specialized to form the bilaminar disc Trophoblast forms: o Part of chorion o Part of placenta This helps in providing oxygen and nutrients and get rid of waste.
  • 16.
    Figure 2. Cleavageof Cells After Fertilization
  • 17.
     Implantation occursin the endometrium of the anterior or posterior wall of the body near the fundus on the 6th day which corresponds to the 20th day of a regular menstrual cycle.  Implantation occurs through four stages e.g. apposition, adhesion, penetration and invasion.  CHANGES IN THE BLASTOCYST: The polar trophoblast cells adjacent to the inner cell mass are primarily involved in adhesion to the endometrial cells.  The factors responsible for blastocyst attachment are: • P. selectin, heparin sulfate, proteoglycan, EGF, integrins, trophinin and others. The signals for trophoblast multiplication arise from the inner cell mass. IMPLANATATION OF THE BLASTOCYST
  • 18.
    continue  ENDOMETRIUM ATTHE IMPLANTATION SITE : (1) The endometrium is in the secretory phase corresponding to 20–21 days of cycle. (2) The microvilli on the surface of the Trophectoderm interdigitate with the decidual cells to form the junctional complexes. Endometrial receptivity and molecular signaling during implantation is induced by progesterone, LIF (leukemia inhibitory factor), prostaglandins and COX-2.
  • 19.
    Four Stages ofImplantation: 1.APPOSITION :  Occurs through pinopod formation. Pinopods are long finger like projections (microvilli) from the endometrial cell surface.  These pinopods absorb the endometrial fluid which is secreted by the endometrial gland cells. This fluid, rich in glycogen and mucin provides nutrition to the blastocyst initially. Unless this fluid is absorbed,adhesion phase cannot occur. 2.Adhesion of blastocyst to the endometrium occurs through the adhesion molecules like integrin, selectin and cadherin (glycoproteins).
  • 20.
    3.PENETRATION: • Actual penetrationand invasion occur through the stromal cells in between the glands and is facilitated by the histolytic action of the blastocyst. With increasing lysis of the stromal cells, the blastocyst is burrowed more and more inside the stratum compactum of the decidua (Fig. 2.5).
  • 21.
    Fig. 2.5: schematicrepresentation showing initial implantation of the blastocyst in the stratum of compactum of the decidua
  • 22.
    Vacuoles appear inthe advancing syncytium which fuse to form large lacunae. These are more evident at the embryonic pole. Concurrently, the syncytial cells penetrate deeper into the stroma and erode the endothelium of the maternal capillaries. The syncytium by penetrating the vessels, not only becomes continuous with the endothelial lining but permits the maternal blood to enter into the lacunar system. Ultimately erosion of few maternal arteries with formation of blood space (lacunae) occurs. Nutrition is now obtained by aerobic metabolic pathway from the maternal blood. Further penetration is stopped probably by the maternal immunological factor and the original point of entry is sealed by fibrin clot and later by epithelium. The process is completed by 10th or 11th day which corresponds to D 24-25 from LMP (Fig. 2.5).
  • 23.
    This type ofdeeper penetration of the human blastocyst is called interstitial implantation and the blastocyst is covered on all sides by the endometrium (decidua). Occasionally, there may be increased blood flow into the lacunar spaces at the a embryonic pole. This results in disruption of the lacunae and extravasation of blood into the endometrial cavity. This corresponds approximately to 13th day after fertilization (at about the expected day of the following period). This may produce confusion in determination of the expected date of delivery. The process of implantation is controlled by the immunomodulatory role of various cytokines (interleukins 3, 4, 5, 6, 10, 13), many local peptides like epidermal growth factor (EGF), insulin like growth factor (IGF) and prostaglandins. Both the decidua and the embryo synthesize these molecules.
  • 24.
    IMPLANATATION OF THEBLASTOCYST • When the cell is implanted in the endometrium, cells start proliferating outside the zona pellucida • The cell membrane will disintegrate. • It forms a fluid-like cytoplasm which consists of the nuclei of the cell. Therefore, the cells lose their well- defined margins • Components of the cell will be released and all of the cytoplasm will fuse together to form a syncytium • This is called the syncytiotrophoblast • At the base of the finger-like structures of the syncytiotrophoblast there are well-defined margins. • This is called the cytotrophoblast
  • 25.
    • Syncytiotrophoblast willcontinue to release hydrolytic enzymes to make its way through the uterine lining. • The uterine lining has maternal blood vessels and the syncytiotrophoblast will move deeper into the endometrium until it becomes confluent with the maternal blood vessels o Now the embryo can receive oxygen, nutrients, hormones, etc. • At day 24, the syncytiotrophoblast starts making β-hCG • It stimulates the corpus luteum to continue producing progesterone o This helps avoid the endometrial lining from shedding like in the normal cell cycles.
  • 26.
    Figure 3. Implantationof the Cell in the Uterus, showing the structure of Trophoblast
  • 27.
    BILAMINAR DISC  Thisis the inner cell mass of the differentiated blastocyst.  It contains 2 sheet like layers (the top and bottom layer) (1) Top layer Called the Epiblast  o Above the epiblast is the amniotic cavity. (2) Bottom layer  Called the Hypoblast  o Below the hypoblast is the yolk sac.
  • 28.
    Figure 4. BilaminarDisc Showing Epiblast and Hypoblast
  • 29.
    (3) From thetop view • On one end of the bilaminar disc (from the top view), there is a depression → prochordal plate o This is an area where the epiblast and hypoblast are fused together. o The prochordal plate helps to give orientation.  As it is located in the cranial side, opposite to the prochordal plate is the caudal side. • On the caudal side, there is a membrane called the cloacal membrane o Becomes the anus • On the cranial side, there is buccopharyngeal membrane o Becomes the mouth
  • 30.
    Figure 5. BilaminarDisc from the top view