Fertilization - Fetal period

FERTILIZATION
 Fertilization is union of a sperm and ovum to form
a zygote
 12 - 24 hours after ovulation at ampulla of oviduct
 Fertilization includes the following phases:
 Passage of sperm through corona radiata
 During coitus about 200-300 million sperm cells are
ejaculated into the vagina
 capacitation of germ cells occur
 Corona radiata is loosened by hyaluronidase enzyme
2. Penetration of zona pellucida
3. Fusion of the oocyte and sperm cell membrane
4. Completion of 2nd meiotic division of 2o oocyte
 female pronucleus is formed
5. Formation of male pronucleus
 tail degenerate
6. Fusion of male & female pronucleus
 results zygote (with 2n chromosomes)
 within 24-48 hours after fertilization EPF in maternal
serum is detected
 When the first sperm enters the egg, the cell
depolarizes causing the release of calcium ions
inside the cell.

 This stimulates the release of granules that cause

changes in the zona pellucida to prevent entry of
other sperm.

 Secondary oocyte completes division, and nuclei

of ovum and sperm unite to form a zygote.
First week of development
Cleavage (Segmentation) of zygote

 Consists of repeated mitotic division of zygote, resulting

in a rapid increase in number of cells (smaller in size)

 Occurs in the oviduct as zygote is still contained in the

zona pellucida.

 It begins about 30 hrs after fertilization as it passes

through the tube.

 The resulting daughter cells are termed as blastomeres.

 At the two cell stage, they
look like twins

 The division continues as 2,

4, 8, 16, . Cells

 12 to 16 blastomeres form
morula at about 3 days after
fertilization.
 Two factors transport zygote into uterus
 Peristaltic contraction of wall of uterine tube
 Ciliary beats of the mucosa of uterine tube

 Morulla is formed of two types of cells

 outer cell mass:- to be future trophoblast
 inner cell mass:- to be future embryoblast
Blastocyst formation

4 days after fertilization spaces appear b/n

blastomeres of the morula

 Fluidspass through zona pellucida into these

cavities from uterine cavity.
 As fluid increases, it separates
the cells into two layers
 outer cell layer, trophoblast
 inner cell mass, embryoblast
 Blastocele: a single cavity
 The embryoblasts form the primordium of the
actual embryo

 The trophoblasts form the primitive organ of

nourishment (chorion)

 Trophoblasts secrete proteolytic enzymes to

degenerate zona pellucida

 The trophoblasts also start to secrete the

hormone, HCG that prepares the uterine wall for
 Spaces fuse to form blastocyst cavity.
 At the end of 4th day the late morulla
contains about 100-150 cells
 At this stage of development, the conceptus
is called blastocyst and differentiate into 2
layers
 an inner cytotrophoblast
 an outer syncytiotrophoblast
 Implantation:- process of blastocyst
embedding into endometrium

 Occur between 5 - 6 to 11 . 12 days along

posterior or anterior wall of uterine body.
Second week of development
Completion of implantation
 B/n 5th & 6th day trophoblastic cells that form
attachment gives polar trophoblasts

 Implantation begins at the end of first week,

continues & is completed during second week.

 The erosive syncytiotrophoblast invades endometrial

stroma to embed blastocyst

 After implantation functional endometrial layer

converted to decidua
 Around 8th day trophoblast in the region of
attachment to the endometrium differentiate
into two cell layers:
1. Inner cellular layer, cytotrophoblast
(Langerhan.s layer)
 Secretes enzymes for degradation of endometrium
during implantation
2. Outer layer consisting of multi-nucleated
syncytiotrophoblasts or plasmodiotrophoblasts
 Degradation of the uterine mucous
membrane releases substances

 These substances released during degradation

are absorbed by syncytiotrophoblasts & serve
as nourishment of the embryo

 Atthis time endometrial stromal cell become

swollen & filled with glycogen called decidual
reaction
 The implantation of blastocyst is completed on
the 10th or 11th day

 Implantation should take place within 36 hours

after the blastocyst contacted the endometrium

 After 36 hours the endometrium considers

blastocyst as foreign & rejects it resulting in
death of embryo
L selectin on trophoblast cells and its
carbohydrate receptors on the uterine
epithelium mediate initial attachment of the
blastocyst to the uterus.
Sites of Implantation
 Most common site is upper, posterior wall of body of
uterus

 Rarely on the anterior wall of uterus

 Implantation can be divided as intrauterine and

extrauterine implantations

 Any implantation site other than the above sites is

termed as abnormal (ectopic) resulting in ectopic
pregnancy
Abnormal implantation

1)Placenta previa:
 Implantation near the internal os.
 The placenta over bridges the os and causes
severe bleeding during later pregnancy &
delivery.

2) Ectopic pregnancy
 implantation out side normal site
 mostly these pregnancies are rejected
 Common Sites of Ectopic Implantations (Ectopic
Pregnancies) include:
1. Tubal
2. Ovarian
3. Abdominal
4. Cervical
5. Vaginal
(rare)
 As implantation progress, a small space appears b/n
inner cell mass and invading trophoblast (beginning
of amniotic cavity)

 Concurrently, morphological changes occur in the

inner cell mass formation of a flattened circular plate
of cells called embryonic disc

 The disc consists of two layers:

 Epiblast:- upper columnar cells
 Hypoblast:- lower cuboidal cells
 Then other cells delaminate from the
cytotrophoblast & form a thin exocoelomic
membrane.

 The cavity now surrounded by this

membrane and hypoblast forming
exocoelomic cavity
 Further delamination of trophoblastic cells
gives rise to a layer of loosely arranged cells
called extraembryonic mesoderm.

 Now the cavity becomes primary yolk sac

 At the same time, isolated spaces called
lacunae appear in the syncytiotrophoblast &
soon become filled with a mixture of blood
(from maternal capillaries) and secretions
from eroded endometrial glands

 Thisnutritive fluid passes to embryonic disc

by diffusion.
A ten-day conceptus is completely embedded
in the endometrium

Extraembryonic mesoderm increase in size &

isolated coelomic spaces appear within it.
These spaces rapidly fuses to form a large
isolated cavity called extraembryonic coelom
Development of Chorion
 Proliferation of cytotrophoblast produces local masses
that extend into syncytiotrophoblast

 This proliferation results primary chorionic villi

 Chorion is extraembronic mesoderm (lining trophoblast

and covering amnion) and trophoblast layers.

 It forms chorionic sac within which the embryo & its

amniotic & yolk sacs are suspended by connecting stalk

 The extraembryonic coelom now is called chorionic

cavity.
Third week of development
Formation of Trilamminar Embryo

 A period of rapid development of embryo

from embryonic disc
 It is characterized by formation of primitive
streak and 3 germ layers as:
 Ectoderm
 Mesoderm
 Endoderm
GASTRULATION

 Isthe process by which the inner cell mass is

converted into trilaminar embryonic disc

 Itbegins at the end of the first week with the

formation of the hypoblast.

 It continues during second week completed

during third week with the formation of 3 germ
layers (ectoderm, mesoderm & endoderm
 The appearance of three layers is known as
gastrulation and the embryo at this time is
known as gastrula
 Amniotic cavity becomes well-developed and
filled with amniotic fluid

 Amnioticfluid is secreted by amniotic cells at

the beginning but later derived from the
mother
 Primitive streak
 Thickened linear band of epiblast.

 Becomes visible by the beginning

of the 3rd wk as a narrow groove
(by invagination of cells).

 Has bulging regions on either side.

 The cephalic end of the streak is

the primitive node surrounding a
primitive pit.
46
 Formation of Primitive Streak
 At the beginning of 3rd
week proliferation &
accumulation of epiblastic
cells in posterior part of the
embryonic disc forms
thickened linear band called
primitive streak.

 It elongates by addition of
cells to its caudal end, and
its cranial end proliferates
to form primitive node 47
 Primitive Streak…

 Concurrently, a narrow primitive groove

develops in the streak.

 Shortly after primitive streak appears cells

leave, its deep surface and form a loose
network of tissue called mesenchyme.

 Some of this tissue soon becomes

embryonic mesoderm.

48
 The epiblast now referred to as embryonic ectoderm and
the hypoblast as embryonic endoderm. By this stage of
development, it is possible to identify the embryo’s:
 craniocaudal axis

 cranial and caudal ends

 dorsal and ventral surfaces

 right and left sides

 Fate of Primitive Streak

 Actively forms mesoderm until the

early part of 4th week

 Then it starts regressing and

becomes an insignificant structure
in the sacrocooccygeal regions

 Normally it degenerates and

disappears by the end of 4th week

 Remnants may persist and give

rise to a large tumor called
Sacrococcygeal Teratomas 50
Notochord
 Is a cellular rod that develops
from notochordal process.

 A rod of mesenchymal cells

located cranially, in the midline,
extending between the primitive
node and the prechordal plate

51
 The Notochord
Steps
1. Primitive pit extends to notochordal process forming a lumen
called notochordal canal
2. The floor of notochordal process fuses with the underlying
embryonic endoderm.
3. The fused region undergoes degeneration.
4. Openings appear in the floor of the notochordal process
5. The openings confluent and floor of notochordal canal
disappear.
6. The remains of notochordal process form a flattened grooved
plate called notochordal plate
7. Beginning from the cranial end, the plate folds to form
notochord 52
Cont….

 The notochord is a structure around which the vertebral

column forms

 It degenerate & disappear when surrounded by vertebral

bodies, but persists as nucleus pulposus of intervertebral disc

o Notochord –induce formation of neural plate - premordium

of CNS.

53
Notochordal plate folds to form the notochord.

54
55
Functions of Notochord
 Defines primordial axis of the embryo
 Provides rigidity to the embryo
 Serves as a basis for the development of the axial skeleton
 Indicates the future site of the vertebral bodies/column
 Regulates differentiation of surrounding structures including
the overlying ectoderm (neural plate) and mesoderm
(somites).
Fate of Notochord
 Degenerates and disappears as the bodies of the vertebrae
develop, but it persists as the nucleus pulposus of each
intervertebral disc
 Remnants of notochordal tissue give rise to tumors called
Chordomas
56
 Formation of the three germ layers
 Cells of the epiblast migrate
toward the primitive streak
they become flask shaped
detach from the epiblast slip
beneath it This inward
movement is known as
invagination.
 Some of the invaginated cells
create:
 Endoderm
 Mesoderm
 Ectoderm
 The epiblast is the source of all
of the germ layers 57
 Primitive streak…

 The first cells to

move inward
displace the
hypoblast to create
the definitive
endoderm.
 Once definitive
endoderm is established,
inwardly moving
epiblast forms
58
 …
 By middle of third week, embryonic mesoderm separate
ectoderm and endoderm completely except:
1. Oropharyngeal membrane cranially
2. Cloacal membrane caudally
3. In the middle cranial to primitive node where
notochordal process extends

59
 NEURULATION

 Process of formation of neural plate, neural folds &

their closure to form neural tube

 Completed by the end of fourth week, when closure

of caudal neuropore occurs

61
Neural plate and neural tube
 As the notochord develops, the embryonic
ectoderm over it thickens to form neural plate

 It is induced by the developing notochord

 Ectoderm of neural plate (neuroectoderm) gives

rise to CNS (brain & spinal cord)
 On about 18th day, the neural plate invaginates
along its central axis to form a neural groove
that has neural folds on each side.

 By the end of 3rd week, the neural folds fuse

converting the neural plate into a neural tube.

 The neural tube soon separates from the

surface ectoderm
64
 The Neural Crest

 As the neural folds fuse to form neural

tube, some neuroectodermal cell lying
along the crest of each neural fold lose
their epithelial affinities & attachments
to neighboring cells.

 As the neural tube separates from

surface ectoderm, these
neuroectodermal cells (neural crest
cells) migrate ventrolaterally on each
side of neural tube.

 They soon form an irregular flattened

mass called neural crest (between
neural tube and surface ectoderm 65
66
 Development of Somites
 As notochord & neural tube form, the
intraembryonic mesoderm on each
side of them thickens to form a
longitudinal column of paraxial
mesoderm

 Toward the end of the third week, the

paraxial mesoderm begins to divide
into paired cuboidal bodies called
somites.
 Somites, located on each side of
neural tube

 Somites give rise to most of the axial

skeleton and associated musculature
68
and adjacent dermis of the skin
The Embryonic Period

4th _
8 Weeks
th

69
 Embryonic period

 All major external and internal structures are established during this
period.

 By the end of this organogenetic period all the main organ systems have
begun develop but function of most organs is minimal.

 Exposure of embryos to teratogens during this period may cause major

congenital anomalies.

 Teratogens are agents such as drugs and viruses that produce or increase
the incidence of congenital anomalies.

 It is the most critical period of development

 As tissues and organs form the shape of the embryo changes, so that by the
70
8th wk the embryo ha s a distinct human appearance.
 Folding of the Embryo

 Folding changes the flat trilaminar embryonic disc into a cylindrical C-

shaped embryo.

 It is due to rapid unproportional growth of embryo.

 Folding at cranial & caudal ends and folding at the sides occur
simultaneously.

 The two ectodermal depressions called cranial & caudal pits appear.

 The cranial pit becomes the oral pit (stomodeum) & separated from gut
tube by oropharyngeal membrane.

 The caudal pit becomes the anal pit (proctodeum) separated from
caudal end of primitive gut by cloacal membrane 71
 Folding of the embryo…
 A significant event in the establishment of body form is folding of the
trilaminar embryonic disc in to somewhat cylindrical embryo.

 Folding results from rapid growth of the embryo, particularly

from the brain and SC.

 Folding at the cranial and caudal ends and at the sides of the
embryo occur simultaneously.

 Concurrently, a relative constriction occurs at the junction of the

embryo and the umbilical vesicle.

 Folding the ends of the embryo ventrally produces head and tail folds
that cause the cranial and caudal regions to move ventrally as the
72
 Folding in median plane
 Occurs in head and tail region.

 Folding results a constriction

between embryo and yolk sac
and the dorsal part of the yolk
sac is incorporated into the
embryo and give rise to
primitive gut.

 The primitive gut is divided

into:
I. Foregut
II. Midgut
74
III. Hindgut
76
 GENERAL CONSIDERATIONS

 By the end of the embryonic period, all major organ

systems have begun to develop, although functionality
may be minimal.

 The development of the cardiovascular system is essential

for obvious reasons, but, in particular, because diffusion
of nutrients by the early uteroplacental circulation can no
longer satisfy the nutritional needs of the rapidly
developing embryo.

80
 Germ Layer Derivatives

 The three germ layers (embryonic ectoderm, mesoderm

and endoderm) which arise from inner cell mass during
3rd week, differentiate into various tissue and organs.

 By the end of embryonic period, the beginnings of all

the main organ systems have been established.

 The cells of each germ layer divide, migrate, aggregate

and differentiate in precise pattern as they form various
organ systems

82
Germ layer derivatives

84
85
 Derivatives of Foregut, Midgut and Hindgut
 The fore gut develops into
 Pharyngeal gut
 Part of respiratory organs
 Esophagus
 Stomach
 Upper part of duodenum
 Liver
 Biliary ways
 Pancreas

 The midgut develops into:

 parts of intestine up to right two-third of transverse colon

 The hindgut develops into:

 the rest part of intestine
86
87
The Fetal Period

9 Week- Birth
th

88
9 -12 Week
th th

 head - half of the crown-ramp length.

 Primary ossification centers appear in the skeleton.

 External genitalia of males and females appear similar

until the end of ninth week, and distinguished at 12
week.

 Urine formation and is excreted into the amniotic fluid.

13th -16th Weeks

 Growth is very rapid during this period

Ossification of skeleton begins

 By 16 week, the ovaries are differentiated and

have many primordial follicles containing oogonia
17th -20th Weeks
 Growth slows down

 Fetal movements are commonly felt by the mother

 The skin is covered with vernix caseosa.

 fatty secretions /fetal sebaceous glands & dead
epidermal cells
 Protects the delicate skin from abrasions and
hardening.
 The body of 20-week fetus is usually completely covered
with fine hair called lanugo, which help holding vernix
caseosa on the skin.

 Brown fat forms during this period.

 By 18 weeks uterus of female fetus is completely

formed.

 By 20 weeks the testes of male fetus begun their descent,

but they are still located on posterior abdominal wall.
21st -25th Weeks

• There is a substantial weight gain

• By 24 week, the secretary epithelial cells

or types II pneumocytes in the
interalveolar walls of the lung have begun
to secrete surfactant (a surface-active lipid
that maintain the patency of the
developing alveoli of the lungs).
26th -29th Weeks

A fetus may survive if born prematurely

and given intensive care because lungs are
capable of breathing air.

Eyes open at the beginning of this period.

Considerable subcutaneous fat has formed.
30th -34th Weeks

Pupillary light reflex can be elicited.

Skin -pink and smooth.

Fatin the body is about 8% of the body

weight.

Descentof testes to the scrotum continue

32 weeks and above usually survive.
35th - 38th Weeks
 35 weeks have a firm grasp & exhibit a spontaneous
orientation to light.
 Slowing of growth

 Fat = 16% of body weight

 Fullterm (38 weeks after fertilization or 40 weeks after

LMP)
 skin:- white or bluish-pink

 chest:- prominent

 testes:- in the scrotum (male)

Twins & Multiple Pregnancies

98
Twins & Multiple Pregnancies

99
 Twins & multiple pregnancies

 Twinning means delivery of 2 or more embryos at the same time.

 In North America (a study result shows the following descriptive
figures)
 Twins occur about 1 in every 90 pregnancies
 Triplets occur about 1 in every 902 pregnancies
 Quadruplets occur about 1 in every 903 pregnancies
 Quintuplets occur about 1 in every 904 pregnancies
 MULTIPLE PREGNANCIES ( Twins, Triples, Quadruples…)
 May develop from multiple ova & abundant spermatozoa =
Dizygotic, multizygotic or plurizygotic
 May develop by splitting of the zygote, morula, or blastocyst =
Monozygotic
100
 TWINS…

 Dizygotic Twins (Fraternal Twins)

 Simultaneous fertilization of two different oocytes by two
different sperms.

 They are not more than siblings, may or may not be of the
same sex
 If they implant nearer to each other, their placenta may fuse.

 Otherwise, they will have separate chorion & amnion

 When their placenta fuse, the blood vessels may anastomose
& blood mixes forming blood group chimesas
101
Dizygotic twins…
 Separate placenta, chorionic
sac and amniotic cavity
 Sometimes two placentas fuse
into one.

 Same or different sex; external

and genetic features are no
more alike than other brothers
or sisters.

 Have 2 amnion, 2 chorion and fused

placenta or separate (some times)
102
103
 Dizygotic twins…
 Same or different sex.

 External and genetic

features are no more
alike than other
brothers or sisters.

104
 Monozygotic (MZ) Twins

 Resulting from a single

fertilized ovum (zygote)
 Splitting of zygote occurs at
various stages of development
 Develop by splitting at
different levels of
development: zygote stage, 2
cell stage, morula, blastocyst,
gastrula, etc.
 Identical twins occur in one-
third of twins
 Same sex and genetically the
same
105
MZ

1. Early Separation
 occur at two cell stage
 blastocyst separately implanted
 has 2 amnion, 2 chorion & 2 placenta
2. Implanted close together
 mostly takes place within one week
 has 2 amnion, 1 chorion & 1 placenta
3. Late Separation
 occur usually by the second week
 has 1 amnion, 1 chorion & 1 placenta
 usually these twins die
 could be found in different forms:
I. Conjoined:- attached at soft parts
II. Parasitic:- one is well-developed but the other is not
III. Separate twins:- each are independent 106
107
 Conjoined/Siamese
 Based on the site of
attachment, conjoined
(Siamese) twins can
be classified as:
1. Thoracopagus
2. Pygopagus
3. Craniopagus
4. Omphalopagus

5. Craniothoracopagus
6. Massive fusion

108
Conjoined Twins…

109
 Monozygotic Twins

 If implanted nearer to each other

they may share placenta, fused
placenta but mixing of blood
does not occur because of the
same gene for blood groups.

 If they implant far away from

each other, they may have
separate placenta, chorion,
amnion, etc.

110
MZ Twins

111
COMPARISON B/N DIZYGOTIC AND MONOZYGOTIC TWINS

112
Superfecundation
 Superfecundation is the fertilization of two or more oocytes at
different times.

 In humans, the presence of two fetuses in the uterus caused by

fertilization at different times (superfecudation) is rare.

 DZ human twins with different fathers have been confirmed by

genetic markers.

113
Reading Assignments

 Fetal membranes
 Placneta
 Formation (placentation)
 Significance
 Barieir (BPB)
 Fetal circulation