General embryology - Copy.pdf

By: Daniel T. (MSc.)
1
He who sees things grow from the beginning will have the
finest view of them. Aristotle, 384-322 BC.

Introduction
 Embryology :- the study of embryos, generally prenatal
development
 Developmental anatomy:- refers to the structural
changes of a human from fertilization to adulthood.
 Teratology (Gr. teratos, monster) is the division of
embryology and pathology that deals with abnormal
development
3

Significance of Embryology
 Bridges the gap between prenatal development and obstetrics,
perinatal medicine, pediatrics, and clinical anatomy
 Develops knowledge concerning the beginnings of human life and
the changes occurring during prenatal development
 Helps to understand the causes of variations in human structure
 Illuminates gross anatomy and explains how normal and abnormal
relations develop
4

Embryologic Terminology
 Oocyte (ovum or egg):- female germ or sex cells
 Sperm (seed):- or spermatozoon, male germ cell
 Zygote:- the union of an oocyte and a sperm during fertilization
 Cleavage:- the series of mitotic cell divisions of the zygote to
form early embryonic cells, blastomeres
 Morula:- solid mass of blastomeres (12 -32) in 3-4 days after
fertilization
 Blastocyst:- the morula enters the uterus and a surrounded by
a fluid-filled cavity, blastocystic cavity
5

 Implantation:- the process during which the blastocyst attaches
to the uterus, and embeds in it.
 Gastrula:- a trilaminar embryonic disc containing the three germ
layers (ectoderm, mesoderm, and endoderm)
 Neurula:- the early embryo during the third and fourth weeks
when the neural tube develops (the first appearance of the nervous
system)
 Embryo :- the developing human during its early stages of
development (56 days)
6

 Conceptus:- The embryo and its associated membranes
(adnexa)
 Primordium:- the beginning or first discernible indication of
an organ or structure
 Fetus:- the developing human after 8 weeks and until birth
 Histogenesis - the differentiation of the specific cells of tissue
and their function
 Organogenesis - formation of organs during development
 Phyliogenesis - the evolutionary development of a species
7

 Embryogenesis :-
o Establishment of the characteristics configuration of the
embryonic body
 Organizers:-
o Are group of cells that induce and determine the differentiation
of adjacent tissue
 Differentiation:-
o The acquisition of one or more characteristics or function
different from that of the original type
8

Human Development
 Human dev’t begins during fertilization
Sperm + oocyte zygote
 Zygote is
o a highly specialized,
o totipotent cell
o contains chromosomes and gene
o unicellular multicellular
 The zygote undergo -
o Cell division
o Cell migration
o Apoptosis
o Differentiation
o Growth
o Cell rearrangement
9

Gametogenesis
 It is the process of formation of female and male gametes.
 Gametes:-
o Are highly specialized sex cells, sperm or egg that unite
with each other to form new organism
o haploid than somatic cell
 There are two types of gametogenesis:
o Oogenesis – female gametogenesis = oocytes
o Spermatogenesis – male gametogenesis = spermatozoa
10

Gametogenesis…
 Gametogenesis involve :
1. Mitosis - to increase the number of primordial germ cells
2. Meiosis - to reduce number of chromosomes
3. Cytodifferentiations - to complete their maturation
Phases of Gametogenesis
o Gametes formation from extra embryonic in origin of germ
cells and migration to gonads.
o Increase number of gametes by mitosis
o Decrease chromosomal material by meiosis
o Structural & functional maturation of gametes 11

Gametogenesis…
 Gametes are derived from primordial germ cells (PGCs) that
are formed in the epiblast during the 2nd week and that
move to the wall of the umbilical vesicle (yolk sac).
 During the 4th week, these cells begin to migrate from the
umbilical vesicle toward the genital ridges (developing
gonads), where they arrive by the end of the 5th week.
 Mitotic divisions increase their number during migration and
also when they arrive in the gonads.
12

Gametogenesis…
 Somatic support cells invest PGC and give rise to
tissues that will nourish and regulate development of
maturing sex cells.
 In females the somatic support cells become ovarian
follicle and in males it become sertoli cells of
seminiferous tubules
13

Diagram showing migration of PGCs to
gonadal ridges
v
14

MEIOSIS
 Meiosis is a special type of cell division that involves
two meiotic cell divisions
 It takes place in germ cells (sperms and oocytes) only.
 Diploid primordial germ cells give rise to haploid
gametes.
15

Meiosis I- reduction division
 Prophase :-DNA replication
D-S chromosome condense
Homologous pair align at the centromere
Chiasma formation
 Metaphase:-chromosome align at the equator
centromere do not replicate
 Anaphase & telophase:-one D-S chromosome of each homologous
pair distributed to each daughter cell
 End with formation of secondary spermatocyte or secondary oocyte
which has the haploid chromosome number (double-chromatid
chromosomes)
16

First
and
second
meiotic
divisions.
A.
Homologous
chromosomes
approach
each
other.
B.
Homologous
chromosomes
pair,
and
each
member
of
the
pair
consists
of
two
chromatids.
C.
Intimately
paired
homologous
chromosomes
interchange
chromatid
fragments
(crossover)
Note
the
chiasma.
D.
Double-structured
chromosomes
pull
apart.
E.
Anaphase
of
the
first
meiotic
division.
F,G.
During
the
second
meiotic
division,
the
double-structured
chromosomes
split
at
the
centromere.
At
completion
of
division,
chromosomes
in
each
of
the
four
daughter
cells
are
different
from
each
other.
17

Meiosis II
 Prophase:- no DNA replication
D-S. chromosome condense
 Metaphase :-chromosome align at the equator.
-centromere replicate.
 Anaphase & telophase:-single strand chromosome is
distributed to each daughter cell.
 Cytokinesis:-cell divide & produce 4 Spermatids in Male
-1 definitive oocyte & 3 polar bodies in Female
- all contain 23 single strand chromosome.
 The second meiotic division is similar to an ordinary mitosis
except that the chromosome number of the cell entering the
second meiotic division is haploid. 18

Importance of meiosis
 Provide constancy of chromosome number by reducing
it to haploid.
 Allow random assortment of maternal and paternal
chromosome between gametes.
 Recombination of genetic material by crossing over.
20

Spermatogenesis
 It is the sequence of events by which spermatogonia are transformed into
mature sperms
 Begins :- 13-16 yrs - old age
 Spermatogonia -mitotic division -primary spermatocytes
 Primary spermatocytes (largest germ cell)-meiosis I - two
haploid secondary spermatocytes
 Secondary spermatocytes-meiosis II -four haploid
spermatids
 Spermatids -spermiogenesis -mature sperm
 Spermiogenesis:-
o condensation of nucleus
o Acrosome formation
o Shading of cytoplasm
o Formation of neck, middle piece, and tail
21

A. Cross section through primitive sex cords of a newborn boy showing primordial germ
cells and supporting cells.
B,C. Two segments of a seminiferous tubule in transverse section. Note the different
stages of spermatogenesis.
Sertoli cells lining the seminiferous tubules support and nurture the
germ cells and are involved in the regulation of spermatogenesis.
23

 The entire spermatogenesis takes about 60-64 days
 Regulation of spermatogenesis is by LH & FSH.
Mature sperm cell is :-actively motile & contain
head ,neck and tail.
24

Mature sperms
 Free-swimming, actively motile cells
 Consists of a head, neck and tail
 The head of the sperm forms most of the bulk of the sperm and
contains the haploid nucleus which is covered by the acrosome.
 Acrosome contain several enzymes that facilitate penetration of the
zona pellucida and corona radiata of the follicular cells during
fertilization
 The tail of the sperm consists :middle piece,
principal and
end piece
 The middle piece contains mitochondria.
25

Mature sperm
Spermiogenesis includes:
• condensation of nucleus
• Shading of cytoplasm
• Acrosome formation
• Formation of neck, middle
piece, and tail and
becomes able to move .
Regulation of spermatogenesis
is by LH & FSH.
26

Oogenesis
 Oogonia transform to mature oocyte.
 It begins in utero (3rd month) completed with sexual maturity
Prenatal maturation of oocyte
 Oogonia enlarge to form primary oocytes before birth.
 Oogonia -mitotic division -primary oocyte
 Primary oocyte surrounded by follicular epithelia i.e. primordial
follicle
 As primary oocyte enlarge, follicular epithelial cell become
cuboidal then columnar forming primary follicle
 Primary oocyte surrounded by glycoprotein material called zona
pellucida
 Primary oocyte begin the first meiotic division but completion of
prophase arrest until puberty
 OMI (oocyte maturation inhibitor) keep meiotic division of
oocyte arrested- secreted by follicular cells 27

Postnatal maturation of oocyte
 Begin during puberty
 The primary oocyte increase in size & shortly before ovulation
complete first meiotic division & form secondary oocyte and first polar
body.
 Secondary oocyte receive almost all cytoplasm
 At ovulation secondary oocyte begin second meiotic division &
progress up to metaphase
 When the sperm penetrate secondary oocyte , second meiotic division
is completed .
 Fertilized oocyte receive most of the cytoplasm
 As polar bodies extruded maturation is completed 30

Number of primary oocytes in different
stages
 5th month = 7 million
 At birth = 700,000 to 2 million
 Beginning of puberty = 400,000
 Ovulated < 500
31

Comparison of male and female gametes
Parameters Oocyte Spermatozoon
Size Massive Tinny cell
Motility Immotile Actively motile
Cytoplasm Abundant Sparse
Sex
chromosome
One kind 23, X Two kind, 23, X and 23, Y
(primary sex
determining)
Miscellaneous Surrounded by zona Has head, neck & tail
pellucida & corona radiata
32

Female Reproductive Organ
 Comprised of :
o Internal genitalia ( uterus, uterine tube ,ovaries and vagina).
o External genitalia ( clitoris, labia majora labia minora,
vestibule, mons pubis)
o Mammary gland
 For understanding of the reproductive cycle and
implantation of the blastocyst
33

Uterus
 Hallow thick walled, pear shaped muscular organ.
 Size ; 7-8 cm length , 2-3 cm thick in non pregnant
 Parts:- Fundus, body, isthmus & cervix
 Wall :- perimetrium myometrium & endometrium
 Layers of Endometrium :- 4-5 mm thick
 During secretory phase of menstrual cycle three layer of endometrium
can be identified microscopically .
 Functional layer- shade during menstruation
thin compact layer:-densely packed CT
thick spongy layer:-edematous CT.
 Basal layer:- is not sloughed off during menstruation
34

The uterine tube
 A long tube that extend from horn of uterus to the peritoneal
cavity.
 Carry oocyte , sperm and zygote
 Parts :- infundibulum ,ampulla ,isthmus & uterine part.
 Length 10- 12 cm, 1cm diameter.
36

Ovaries
 Paired primary sex organs, pinkish white oval
structure
 Almond-shaped organ nestled in the ovarian fossa
 Produce the female gametes (ova) and secrete female
hormones estrogen and progesterone.
 It expel oocyte to peritoneal cavity.
 Measures about 3 cm long, 1.5 cm
wide, and 1 cm thick
37

The Female Sexual Cycle
 It is repetitive changes that take place in the female
reproductive organs during her reproductive life.
 Begins at puberty and continues until menopause
 Prepare reproductive organ for pregnancy.
 The first menstrual flow is called menarche
 Average of menarche is 12 yrs (9-16yrs)
38

Cont…
 It involves hypothalamus , pituitary gland ,ovaries,
uterus,uterine tubes, vagina, and mammary glands
 Hypothalamus--- GnRH--- pituitary --- LH & FSH.
 FSH :-dev’t of ovarian follicle & estrogen production
 LH:-ovulation & progesterone production.
 The female sexual cycle has two major phases:
1. Ovarian cycle (follicular, ovulatory & luteal phases)
2. Endometrial cycle (menstrual, proliferative & secretory
phases)
39

A. Ovarian cycle
 Has three phases:
o Follicular phase
o Ovulatory phase
o Luteal phase
1. The follicular phase (5th to 13th day) following menses
 Several primordial follicles accumulated in the cavity antrum,
rich in estrogen start to grow at the beginning of the monthly
cycle.
 The primary follicles start to produce follicular fluid called
liquor folliculi.
 On the 6th day, a mature follicle called Graafian follicle is
formed that develops into mature ova.
 This phase is under the regulation of pituitary hormones- FSH
& LH
40

Cont…
 It is characterized by :-
o Growth & differentiation of primary oocyte.
o Proliferation of follicular cells
o Formation of zona pellucida
o Development of the theca folliculi
41

Ovarian cycle …cont’d
2. Ovulation phase (14th to 15th day)
o The wall of the graafian follicle ruptures and
o The ovum, zona pellucida and one layer of the corona radiata are shed into
the peritonial cavity.
Mechanism of ovulation:
o LH is the hormone of ovulation
o 36 hrs before ovulation, APG produces large amount of LH through
positive feed back (LH surge) → LH reaches peak level 12 hrs before
ovulation.
o ↑LH→ ↑antral fluid volume → ↑progesterone secretion → ↑BF to the
graafian follicles → ↑follicular swelling → ↑pressure →rupture →release
of ovum. 42

Graafian
follicle
bulge on
the ovary
surface.
The
beginning
formation
of a
stigma
(whitish
region
free of
blood
vessels).
1. Fallopian
tube
2. Fimbriae
3. Ovary
4. Follicle
5. Stigma
43

Cont…
 The principle mechanism leading to expulsion of
oocyte is:
Raised intrafollicular pressure
Contraction of smooth muscles in theca externa
Enzymatic digestion of follicular wall
Increased FSH production from pituitary gland
Completion of first meiotic division of primary
oocyte
46

Ovarian cycle 1. Follicular phase/estrogen
phase/preovulatory phase
2. Ovulation
3 Progestational phase.
Luteal /postovulatory/
Graafian follicles
Theca follicles
Thecca interna
Theca externa
47

3. The Luteal phase (15th to 25th day)
o After the rupture of the graafian follicle and shedding of the
ovum, the remaining part of the graafian follicle collapses.
o Under the influence of LH, the granulosa cells hypertrophied
and proliferated to be transformed into corpus luteum.
o Types:- corpus luteum of pregnancy
corpus luteum of menstruation
o Function of corpus luteum is:
 Secretion of ↑↑progesterone and ↑estrogen and
 Maintain the pregnancy
48

Cont…
 Corpus luteum of pregnancy:-
o formed if ovum is fertilized
o It enlarge and increase its hormone production
o hCG prevent its degeneration
o Functionality - 20wks of pregnancy
 Corpus luteum of menstruation
o formed if the ovum is not fertilized
o Degenerate 10-12 days after ovulation
o Subsequently changed to corpus albicans
49

After ovulation, the corpus luteum undergoes 4 stages:
1. Stage of vascularization/corpus hemorrhagicum:
 Vascularization of granulosal cells
2. Stage of glandular metamorphosis:
 Follicular granulosal and theca cells are transformed
into luteal cells
oWhich can concentrate cholesterol as a temporary glandular
cells.
50

3. Stage of full development of corpus luteum:
 ↑↑progesterone and ↑estrogen secretion.
 The fate of corpus luteum depends on 2 factors
a.If fertilization occurs, corpus luteum stays active for more
than 10 days (by human chorionic gonadotropin (hCG))
b.If no fertilization occurs, corpus luteum stays active for 10
days and then degenerated.
4. Stage of envolution:
 Luteal cells are replaced by fibrous tissues, transformed into corpus
albicanus.
51

Menstrual ( endometrial )cycle
 A cyclic changes in the endometrium
 Regulated by estrogen and progesterone
 Activities - oocyte; matures, ovulated, and enters the
uterine tube
Phases of the Menstrual Cycle
52

Endometrial Cycle
• 3 phases which are regulated by
Ovarian hormones
1. Bleeding(menstrual) phase
(3-5 days)
– Desquamation of the functional
layer
– Loss of 50 ml (30-80 ml) of
blood
– Caused by sudden withdrawal
of sex hormones
– Menstruation
3. Secretory phase(15-28)
(Progestational phase)
– Glands become secretory
– Arteries become more
spiral
– Thickness = 6 mm
– Caused by progesterone &
estrogen
2. Proliferative phase(5-14 days)
 Growth & development of endometrial glands
 Proliferation of endometrial stromal cells
 Growth of spiral arteries
 regulated by estrogen
53

Ovarian
cycle
Endometrial
cycle
54

Table 1. phases of menstrual cycle
Phases Activities Hormones Duration
Menstrual Functional layer sloughed off & LH decreased = no 4-5 days
discarded progesterone
Proliferative
( estrogenic /
follicular )
-Thickness of endometrium increases
2-3 fold
-Growth of ovarian follicle
- length ning of gland îes
-Spiral aa elongate
Estrogen under 9 days
FSH
Secretory / - glands become wide, tortuous & -progesterone & 13 days
Luteal saccular- secrete glycogen estrogen
-endometrium thickens -FSH & LH-
-spiral aa grow into the compact layer ovulation
& increasingly coiled
Ischemic Corpus luteum degenerate
spiral aa constricted
Loss of interstitial fluid Decreased
Glandular secretion stop progesterone
Marked shrinkage of endometrium
Pregnancy 0ccur if there is Px 55

Transportation of gametes
Oocyte transport
 Oocyte :- is by sweeping action of fimbriae
- fluid current of cilia in the fimbriae
-peristalsis movement of wall of oviduct
56

Sperm Transport
 From epididymis to urethra
by peristalsis movement of
vas deference
 Contraction of urethral
muscle
 200 to 600 million sperms
deposited in uterus and vagina
 Vesiculase-coagulate semen
& form vaginal plug.
 Muscular contraction of
uterus & oviduct
 Prostaglandins- present in the
seminal plasma may
stimulate uterine motility at
the time of intercourse
 Fructose –energy source 57

Conditioning of the Sperms
 The sperms in the female genital tract, before fertilization undergo
1. Capacitation
2. Acrosome reaction
Capacitation:-
 Glycoprotein coat and seminal proteins are removed from the surface of
the sperm's acrosome
 Occur in the uterus & uterine tubes.
 It takes about 7 hours.
 Capacitated sperms show no morphological change, but more active
 Completion of capacitation permits acrosome reaction to
occur.
59

Acrosome reaction
 During which acrosin- and trypsin-like substances are released to penetrate
the zona pellucida.
 Occurs during passage of sperm through corona radiata.
 Outer membrane of the acrosome fuses with overlying cell
membrane of sperm head.
 Fused membranes then rupture, producing multiple perforations
1. Hyaluronidase: needed to assist in penetration of the corona radiata
barrier;
2. Trypsin-like substances: needed for the digestion of the zona
pellucida;
3. Acrosin: also needed to help the sperm cross the zona pellucida.
4. Progesterone (present in follicular fluid) seems to stimulate the
acrosome reaction. 60

1, Sperm during capacitation, a period of conditioning that occurs in the female reproductive
tract. 2, Sperm undergoing the acrosome reaction, during which perforations form in the
acrosome. 3, Sperm digesting a path through the zona pellucida by the action of enzymes released
from the acrosome. 4, Sperm after entering the cytoplasm of the oocyte
61

Fertilization
 Complex sequence of events
 Begins with contact between a sperm and a secondary oocyte
 Ends with the intermingling of the maternal and paternal
chromosomes and form a Zygote.
 Defects at any stage in the sequence of these events might
cause the zygote to die.
 Usually takes place 12 hours after ovulation
 The usual site of fertilization is the ampulla of the uterine
tube, its longest and widest part. 62

Phases of Fertilization
 Passage of sperm through
corona radiata by the help
of
o Hyaluronidase from
acrosome
o Sperm tail
o Tubal mucosal enzymes
 Penetration of zona pellucida
facilitated by
o Acrosin
o Neuraminidase
o Esterase
 Zona reaction
o Lysosomal enzymes of
cortical granules
o Prevent polyspermy 63

Phases of Fertilization
 Fusion of plasma membranes
of secondary oocyte and
sperm
o head and tail of the sperm
enter the cytoplasm of the
oocyte
 Completion of 2nd meiotic
division of oocyte and
formation of female
pronucleus
 Formation of male
pronucleus.
 Ootid
 Fusion of pronuclei to form
Zygote
o chromosomes in the zygote
become arranged on a
cleavage spindle
64

Fate of Fertilization
1. Stimulates the penetrated oocyte to complete the second
meiotic division.
2. Restores the normal diploid number of chromosomes (46)
in the zygote.
3. Results in variation of the human species through mingling
of maternal and paternal chromosomes.
4. Determines chromosomal sex of the embryo.
5. Causes metabolic activation of the ootid and initiates
cleavage (cell division)of the zygote.
6. Perpetuation of species
66

Cleavage of Zygote
67
 Within 24 hours after fertilization, the zygote initiates a rapid series
of mitotic cell divisions called cleavage.
 This results in rapid increase in number of cells.
 These divisions are not accompanied by cell growth, so they sub-
divide the large zygote into many smaller daughter cells called
blastomeres.
 The embryo as a whole does not increase in size during cleavage
and remains enclosed in the zona pellucida.
 Occurs as the zygote passes along the uterine tube toward the uterus

Cont…
 Until the 8-cell stage, they form a loosely arranged clump
 After that, blastomeres form a compact ball of cells.
 Compaction permits greater cell-to-cell interaction and is a
prerequisite for segregation of the internal cells that form the
embryoblast (inner cell mass) of the blastocyst
 3 days after fertilization, when there are 12 to 32
blastomeres, the developing human is called a morula.
 Internal cells of the morula are surrounded by
trophoblastic cell 69

70
Illustrations of a cleaving zygote and formation of the blastocyst. A to D,
Various stages of cleavage of the zygote. The period of the morula begins
at the 12-cell to 32-cell stage and ends when the blastocyst forms.

Formation of Blastocyst
 Shortly after the morula enters the uterus (approximately 4 days
after fertilization), a fluid-filled space, the blastocystic cavity,
appears inside the morula
 The fluid passes from the uterine cavity through the zona
pellucida to form this space.
 As fluid increases in the blastocystic cavity, it separates the
blastomeres into two parts:
o A thin, outer cell layer, the trophoblast, which gives rise to the
embryonic part of the placenta
o A group of centrally located blastomeres, the embryoblast,
which gives rise to the embryo 71

Cont…
 At this time, the embryo is
a blastocyst.
 The side of the blastocyst
containing the inner cell
mass is called the
embryonic pole of the
blastocyst.
 The opposite side is called
the abembryonic pole. 72

Cont…
 The embryoblast now projects into the blastocystic cavity and the
trophoblast forms the wall of the blastocyst.
 After the free blastocyst has floated in the uterine secretions for
approximately 2 days, the zona pellucida gradually degenerates and
disappears.
 Shedding of the zona pellucida permits the hatched blastocyst to increase
rapidly in size.
 While floating in the uterus, this early embryo derives nourishment from
secretions of the uterine glands.
73

Zona Pellucida - Functions
74
 Prevent implantation of blastocyst at sites other than the
normal.
 Prevents premature implantation
 Species-specific sperm penetration
 Permanent block to polyspermy
 Acts as a porous selective filter - uterine tube signals
 Immunological barrier (histocompatibility antigens)
 Keeps blastomeres together

Cont…
 The blastocyst enters the
uterus at about 6 days after
fertilization.
 The blastocyst attaches to the
endometrial epithelium
(Implantation), usually
adjacent to the embryonic
pole on day 6.
 By the time the embryo
reaches the uterine cavity, it’s
in the form of a blastocyst.
75

Cont…
 As soon as it attaches to the endometrial epithelium, the trophoblast
starts to proliferate rapidly and gradually differentiates into two
layers:
o An inner layer of cytotrophoblast
o An outer layer of syncytiotrophoblast consisting of a multinucleated
protoplasmic mass in which no cell boundaries can be observed
 At approximately 6 days, the fingerlike processes of
syncytiotrophoblast extend through the endometrial epithelium and
invade the connective tissue.
76

Cont…
 By the end of the first week, the
blastocyst is superficially
implanted and is deriving its
nourishment from the eroded
maternal tissues
 At approximately 7 days, a layer
of cells, the hypoblast (primary
endoderm), appears on the
surface of the embryoblast
facing the blastocystic cavity
77

Events during the first week
78

Formation of the Bilaminar Embryonic Disc:
Second Week
 Implantation of the blastocyst is completed during the second week(6-10
days).
 Morphologic changes in the embryoblast produce a bilaminar embryonic
disc composed of epiblast and hypoblast.
 The embryonic disc gives rise to the germ layers that form all the tissues
and organs of the embryo.
 Extra-embryonic structures forming during the second week are:
o Amniotic cavity
o Amnion
o Umbilical vesicle (yolk sac)
o Connecting stalk and
o Chorionic sac. 80

Completion of Implantation of Blastocyst
 As the blastocyst implants more trophoblast contacts the
endometrium and differentiates into two layers:
o An inner layer, cytotrophoblast, that is mitotically active and
forms new cells that migrate into the increasing mass of
syncytiotrophoblast, where they fuse and lose their cell
membranes
o The syncytiotrophoblast, a rapidly expanding, multinucleated
mass in which no cell boundaries are discernible
 The erosive syncytiotrophoblast invades the endometrial
connective tissue, and the blastocyst slowly becomes embedded in
the endometrium 81

Cont…
 Cells of the inner cell mass or embryoblast also differentiate into
two layers:(day 7)
o A layer of small cuboidal cell adjacent to the blastocyst
cavity, known as hypoblast layers
o A layer of high columnar cell adjacent to the amniotic
cavity, the epiblast layer
o Together the layers form a flat bilaminar disc
 At the same time, small cavity appears within the epiblast.
 This cavity enlarges to become the amniotic cavity
83

84
o Implantation of a blastocyst in the
endometrium. The actual size of the
conceptus is 0.1 mm, approximately the
size of the period at the end of this
sentence.
o A, Drawing of a section through a
blastocyst partially embedded in the
uterine endometrium (approximately 8
days). Note the slit-like amniotic cavity.
o B, Drawing of a section through a
blastocyst of approximately 9 days
implanted in the endometrium. Note the
lacunae appearing in the
syncytiotrophoblast.

Day 9 &10
 The blastocysts more deeply embedded in the endometrium, the
penetration defect in the surface epithelium is closed by a fibrin
coagulum.
 At the abembryonic pole, flattened cell probably originated from
hypoblast form a thin membrane, the exoceolomic (Heuser’s)
membrane.
 This membrane together with the hypoblast, forms the lining of
exocelomic cavity or primitive yolk sac.
 Lacunae - appear in the syncytiotrophoblast = primordial
uteroplacental circulation
 Lacunae communicate with endometrial capillaries. 85

86
Embedded blastocysts.
A, 10 days.

Day 11 & 12
 Cells from the vesicle
endoderm form
extraembryonic mesoderm
 Extraembryonic coelom, form
in extraembryonic mesoderm
o extraembryonic somatopleuric
mesoderm
o extraembryonic splanchnopleuric
mesoderm
 Lacunar network
 Uterine wall defect completely
heal ( day 12)
87

Day 13
 Secondary umbilical vesicle formed
 Cytotrophoblastic cellular projections
form primary chorionic villi
 Extraembryonic coelom is now called the
chorionic cavity
 Extraembryonic mesoderm lining the
inside of the cytotrophoblast is
known as chorionic plate
 Connecting stalk, future umbilical cord,
connect extraembryonic mesoderm to the
chorionic cavity
88

Day 14
 Prechordal plate
o develops as a localized
thickening of the hypoblast
o future site of the mouth
o an important organizer of the
head region.
o It helps to establish the bilateral
symmetry of the embryo.
o It helps to establish the cranial
versus the caudal region of the
embryo.
90

2nd week of dev’t is known as the week of 2’s
91
 The trophoblast differentiate into two layers; cytotrophoblast
and syncytiotrophoblast
 The embryoblast forms two layers; epiblast and hypoblast
 The extraembryonic mesoderm splits into two layers; somatic
and splanchnic layers
 2 cavities forms; amniotic and yolk sac cavities

92
Origin of embryonic tissues. The colors in the boxes are used in drawings of sections of
embryos.

Third Week of Development
 Is the period of formation of germ layers and early tissue and organ
differentiation
 Characterized by
o Appearance of primitive streak
o Development of notochord
o Differentiation of three germ layers
 Coincides with the week following the first missed menstrual period;
that is, 5 weeks after the first day of the LNMP.
o Cessation of menstruation is often the first indication that a woman
may be pregnant.
 Normal pregnancy can be detected with ultrasonography. 94

GASTRULATION
 A process by which 3 germ layers are formed
 Axial orientation are established
 Bi-laminar embryonic disc is converted into a tri-laminar embryonic
disc.
 Extensive cell shape changes, rearrangement, movement, and changes
in adhesive properties facilitate gastrulation.
 Beginning of morphogenesis.
 Begins with formation of the primitive streak on the surface of the
epiblast.
 The epiblast, through the process of gastrulation, is the source of all of
the germ layers. 95

Primitive Streak
 Thickened linear band of epiblast in the median plane of the dorsal
aspect of the embryonic disc (15- to 16-day).
o Due to proliferation and movement of cells of the epiblast to the
median plane of the embryonic disc.
 The cephalic end of the streak, the primitive node surround the
primitive pit.
 As soon as the primitive streak appears,
it is possible to identify
o the embryo's cranio-caudal axis,
o its cranial and caudal ends,
o its dorsal and ventral surfaces, and its right and left sides 96

Cont…
 Shortly after the primitive streak appears, cells leave its deep
surface and form mesenchyme (ameboid and actively phagocytic
cells)
 Some mesenchyme forms mesoblast, which forms the
intraembryonic, or embryonic mesoderm.
 Cells from the epiblast as well as from the primitive node and other
parts of the primitive streak displace the hypoblast, forming the
embryonic endoderm in the roof of the umbilical vesicle.
 The cells remaining in the epiblast form the embryonic ectoderm
97

o A, Drawing of a dorsal view of a 16-day embryo. The amnion has
been removed to expose the embryonic disc.
o B, Drawing of the cranial half of the embryonic disc. The disc has
been cut transversely to show the migration of mesenchymal cells
from the primitive streak to form mesoblast that soon organizes to
form the intraembryonic mesoderm
98

Fate of Primitive Streak
 The primitive streak normally
degenerate and disappears by
the end of the fourth week
 If primitive streak persist
beyond 4th week give rise to
tumor
 Sacrococcygeal
teratoma
99

Notochordal process and notochord
 Mesodermal cell migrate cranially from the primitive node and
pit, forming a median cellular cord is called the notochordal
process
 This process acquires a lumen, the notochordal canal
 The notochordal process grows cranially up to prechordal plate,
area of contact b/n ectoderm and endoderm
 The prechordal plate is the primordium of the oropharyngeal
membrane, future site of the oral cavity
100

101
Illustrations of developing
notochordal process. The small
sketch at the upper left is for
orientation.
A, Dorsal view
of the embryonic disc
(approximately 16 days) exposed
by removal of the amnion. The
notochordal process is shown as if
it were visible through the
embryonic ectoderm.
B, C, and E, Median sections at the
plane shown in A, illustrating
successive stages in the
development of the notochordal
process and canal. The stages
shown in C and E occur at
approximately 18 days.
D and F, Transverse sections
through the embryonic disc at the
levels shown in C and E.

Cont…
 Cells with mesodermal fates
migrate cranially on each side
of the notochordal process and
meet the prechordal plate to
form cardiogenic mesoderm in
the cardiogenic area
 Caudal to the primitive streak
there is a circular area called
cloacal membrane, the future
site of the anus
102

NOTOCHORD
 Rodlike cellular structure formed from notochordal precursor cells
when induced by primitive streak
 Extends from the oropharyngeal membrane to the primitive node
 Degenerates as the bodies of the vertebrae form, but small portions
of it persist as the nucleus pulposus of each IV disc and apical
ligament of dense.
 Notochord:
o Define primordial axis of the embryo and gives its rigidity
o Serve as the base for the development of axial skeleton
o Indicates the future site of vertebral bodies
o Primary inductor of neural plate 103

DEVELOPMENT OF NOTOCHORD
 Notochordal process elongates by invagination of cells from the
primitive pit
 The primitive pit extend in to the notochordal process forming
notochordal canal
 The notochordal process is now cellular tube that extends cranially
from the primitive node to prechordal plate
 The floor of notochordal process fuse with the underlying
embryonic endoderm
 The fused layers gradually undergo degeneration and form
openings in the floor of notochordal process which brings the
notochordal canal in to communication with yolk sac
104

105
Illustrations of notochord
development by
transformation of the
notochordal process. A,
Dorsal view of the
bilaminar
embryonic disc at 18 days,
exposed by removing the
amnion. B, Three-
dimensional median
section of the embryo. C
and E, Similar
sections of slightly older
embryos. D, F, and G,
Transverse sections of the
trilaminar embryonic disc
at the levels shown in C
and E.

Cont…
 The opening becomes confluent, and the floor of the notochordal
canal disappears, the remains of notochordal process form
notochordal plate
 Beginning at the cranial end the notochordal cells proliferate and
notochordal plate infolds to form the notochord
 The proximal part of notochordal canal persist temporarily as a
neurentric canal which disappear when notochord is completely
formed
 Notochord become detached from the endoderm of yolk sac,
which again becomes a continuous layer.
106

A. Drawing of a sagittal section through a
17-day embryo. The most cranial portion
of the definitive notochord has formed,
while prenotochordal cells caudal to this
region are intercalated into the
endoderm as the notochordal plate.
B. Schematic cross section through the
region of the notochordal plate. Soon the
notochordal plate will detach from the
endoderm to form the definitive
notochord.
C. Schematic view showing the definitive
notochord.
107

The Allantois
 Small out-pouching from the caudal wall of the umbilical vesicle around
the 16th day of development
 Function:-
o In reptiles, mammals and birds
 Reservoir for excretion products of the renal system
 Respiratory function
o In humans
 Blood formation occurs in its wall during the 3rd -5th weeks.
 Its blood vessel become the umbilical arteries and vein
 The proximal part persists as the urachus,
 The urachus is represented in adults by the median umbilical ligament
108

Neurulation: formation of the neural
tube
 Notochord induces the embryonic ectoderm to thicken and form
an elongated plate of thickened epithelial cells, the neural plate
 By 18th day, the neural plate invaginates along its central axis
to form neural groove, which has neural folds on each side
110

Neurulation
 By the end of the third week, the neural folds fuse and convert the neural
plate into a neural tube, the primordium of the CNS
 As the neural folds meet,
o Neural tube separates from the surface ectoderm
o Neural crest cells changes from epithelial to mesenchymal and
migrate to the surface ectoderm
o Surface ectoderm differentiates into the epidermis
o Neural crest cells form a flattened irregular mass, the neural crest
o Neural crest cells give rise to sensory ganglia of the spinal and
cranial nerves, ganglia of the autonomic nervous system, Schwann
cells, cells of the adrenal medulla. 111

Diagrammatic
transverse sections
through progressively
older embryos
illustrating formation
of the
neural groove,
neural folds,
neural tube,
and
neural crest.
112

 The cranial open end of the
tube is the anterior (rostral)
neuropore, and the caudal
open end of the tube is the
posterior
(caudal) neuropore
 Rostral neuropore close at day
25 and the posterior
neuropore
closes at day 27
 Neural tube defects -occur if
the pores are not closed
timely 113

Neural crest cells give rise to
 The spinal ganglia (dorsal root ganglia) and the ganglia of
ANS.
 The ganglia of CN V, VII, IX, and X
 Neurolemma sheaths of peripheral nerves and contribute to
the formation of the leptomeninges.
 Contribute to the formation of pigment cells, the
suprarenal medulla, and CT of the head.
114

Development of Somites
 In addition to the notochord, cells derived from the primitive node
form paraxial mesoderm.
 Continuous laterally with the intermediate mesoderm, which
gradually thins into a layer of lateral mesoderm.
 The lateral mesoderm is continuous with the extraembryonic
mesoderm covering the umbilical vesicle and amnion.
 Toward the end of the third week, the paraxial mesoderm
differentiates, condenses, and begins to divide into paired cuboidal
bodies, the somites, which are located on each side of the
developing neural tube
115

Development of Somites
 Form in a cranio-caudal sequence
 The first pair of somites appears at
the end of the 3rd week
 38 pairs at (days 20 to 30), 42 to
44 pairs at the end of the 5th week
 Used for determining an embryo's
age
116

Cont…
 Somites first appear in the future occipital region of the
embryo.
 They soon develop cranio-caudally and give rise to most of the
axial skeleton and associated musculature as well as to the
adjacent dermis of the skin.
 Cranial somites are the oldest and caudal somites are the
youngest.
118

Fate Map Established During Gastrulation
 Regions of the epiblast that migrate an ingress through the
primitive streak have been mapped, and their ultimate fates
have been determined. For example,
o Cells that ingress through the cranial region of the node
become notochord;
o Those migrating at the lateral edges of the node and from
the cranial end of the streak become paraxial mesoderm;
119

Cont…
 Cells migrating through the midstreak region become
intermediate mesoderm;
 Those migrating through the more caudal part of the
streak form lateral plate mesoderm; and
 Cells migrating through the caudal most part of the
streak contribute to extraembryonic mesoderm.
120

Development of the intraembryonic coelom
 The primordium of intraembryonic coelom or embryonic body
cavity appears as isolated coelomic spaces in the lateral mesoderm
and cardiogenic area
 Spaces coalesce and form horse-shoe shaped cavity
intraembryonic coelom
 Intraembryonic coelom divides the lateral mesoderm in to
o Somatic or parietal layer_ embryonic body wall
o Splachnic/ visceral layer _ embryonic gut
 Intraembryonic coelom give rise to Pericardial, Pleural and
Peritoneal cavities = 2nd month 121

Early development of the cardiovascular system
 At the end of the second week
there is urgent need for blood
vessels to bring blood to the
embryo from the maternal
circulation
 During the third week, a
primordial utero-placental
circulation develops
123

Blood vessel formation
 Begins in the extraembryonic mesoderm of the umbilical vesicle,
connecting stalk, and chorion
 Embryonic blood vessels begin to develop approximately 2 days
later
 Embryonic b/v formation involves two processes
o Vasculogenesis :- the formation of new vascular channels by
assembly of individual cell precursors, angioblasts
o Angiogenesis :- the formation of new vessels by
budding and branching from pre-existing vessels
124

Steps of vasculogenesis
 Mesenchymal cells (mesoderm derived)--angioblasts--blood islands,
associated with the umbilical vesicle or endothelial cords within the
embryo
 Confluence of intercellular clefts result small cavities within the blood
islands and endothelial cords
 Angioblasts flatten to form endothelial cells that arrange themselves
around the cavities in the blood island to form the endothelium.
 These endothelium-lined cavities soon fuse to form networks of
endothelial channels (vasculogenesis).
 Vessels sprout into adjacent areas by endothelial budding and fuse with
other vessels
125

Primordial CVS
 Heart and great vessels arise from mesenchymal cells in the
cardiogenic area
 Paired longitudinal endothelial lined channels - endocardial
heart tubes develop and fuse to form primordial heart tube
 Tubular heart join with blood vessels in the embryo, connecting
stalk, chorion, and yolk sac to form primordial CVS
 On 21st day blood circulation begin and heart begin to beat
 CVS is the 1st organ system to reach its functional state
127

Development of Chorionic Villi
 Primary chorionic villi _ end 2nd week
 Secondary chorionic villi_ early 3rd week
o branched and contain core mesenchymal tissue
 Tertiary chorionic villi
o Mesenchymal cell differentiate in to blood vessels
o Blood vessels are visible
o Capillaries fuse and form arterio-capillary networks
o Connected to embryonic heart
 Stem cells/ anchoring villi/ attach to endometrium
 Terminal villi side branches of stem villi
o main exchange of material between mother and developing embryo.
129

130
Diagrams illustrating
development of secondary
chorionic villi into tertiary
chorionic villi. Early formation of
the placenta is also shown.
A, Sagittal section of an embryo
(approximately 16 days).
B, Section of a secondary
chorionic villus.
C, Section of an implanted
embryo (approximately 21 days).
D, Section of a tertiary chorionic
villus. The fetal blood in the
capillaries is separated
from the maternal blood
surrounding the villus by the
endothelium of the capillaries,
embryonic connective tissue,
cytotrophoblast,
and syncytiotrophoblast.

Fourth to Eighth Weeks:- Period
of organogenesis
Major event
 Development of main organ systems from the three germ layer but
not fully functional except for the cardiovascular system
 Folding of the embryo and acquiring distinctly human appearance
 Risk period to develop congenital anomalies if exposed to
teratogens.
133

 Human development may be divided into three phases, which to
some extent are interrelated:
o Growth, which involves cell division and the elaboration of
cell products.
o Morphogenesis ,development of shape, size, or other
features of a particular organ or part or the whole of the body.
o Differentiation, maturation of physiologic processes.
 Completion of differentiation results in the formation of tissues
and organs that are capable of performing specialized functions.
Phases of Embryonic Development
134

Folding of the Embryo
 Folding changes the flat tri-laminar embryonic disc into a
cylindrical c-shaped embryo
 It is due to rapid un-proportional growth of embryo
 Occurs in median and horizontal planes
Folding in median plane
 Occurs in head and tail region
 Folding results in 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 135

Folding in the median plane
A) Head fold
 Because the forebrain growing beyond the oropharyngeal
membrane and overhanging the developing heart and results in:
o Primitive heart and oropharyngeal membrane move caudally
and ventrally.
o Part of the yolk sac is incorporated into the embryo forming
the foregut.
136

Folding of cranial end of embryo.
Note that the septum transversum,
primordial heart, pericardial coelom,
and oropharyngeal membrane have
moved onto the ventral surface of the
embryo. Observe also that part of the
umbilical vesicle is incorporated into
the embryo as the foregut. 137

Folding in the median plane
B) Tail fold
 Because of growth of the spinal cord and results in:
o Tail region projects over the cloacal membrane
o Part of the yolk sac is incorporated into the embryo forming
the hindgut
o Connecting stalk and allantois moves to the ventral aspect.
o Allantois is partly incorporated into the embryo.
138

Folding of caudal end of the embryo.
A, Lateral view of a 4-week embryo.
B, Sagittal section of caudal part of the embryo at the
beginning of the fourth week.
C, Similar section at the end of the fourth week. Note
that part of the umbilical vesicle is incorporated into
the embryo as the hindgut and that the terminal part of
the hindgut has dilated to form the cloaca. Observe
also the change in position of the primitive streak,
allantois, cloacal membrane, and connecting stalk. 139

Effects of cranio-caudal folding
 Before folding, the structure seen in
the midline from the cranial to
caudal side are
o septum transversum,
o pericardial cavity and heart
o prechordal plate
o neural plate/fold
o primitive streak
o cloacal membrane.
140

Cont…
 After folding, the relative positions of these structures changes to:
o With the formation of the head fold, the developing
pericardial cavity comes to lie on the ventral side of the embryo,
ventral to the gut
o The heart, which was developing in the pericardial cavity, now lies
in the roof of the cavity
o The pericardial coelom lies ventral to the heart and cranial to the
septum transversum
o The septum transversum now lies caudal to the
heart, later develop in to central tendon of the diaphragm.
141

Drawings of the effect of the
head fold on the
intraembryonic coelom.
A, Lateral view of an embryo
(24 to 25
days) during folding, showing
the large forebrain, ventral
position of the heart, and
communication between the
intraembryonic and
extraembryonic parts of the
coelom.
B, Schematic drawing of an
embryo (26 to 27 days) after
folding, showing the
pericardial cavity
ventrally, the
pericardioperitoneal canals
running dorsally on each side
of the foregut, and the
intraembryonic coelom in
communication
with the extraembryonic
coelom. 142

Folding in the horizontal plane
 As right and left lateral folding taking place in this plane and
results in:
o Abdominal wall is formed when the folds fuse
o Mid-gut is formed by incorporation of yolk sac and
temporarily connected by the yolk stalk (omphalo-
mesenteric or vitelline duct)
o The amniotic cavity expands and obliterates the chorionic
cavity and amnion forms epithelial covering of the umbilical
cord.
143

144
Drawings of folding of embryos during the fourth week

Anterior Body Wall Defects
 Failure of the anterior (ventral) body wall to form properly during body
folding or subsequent development results in anterior body wall
defects.
 The most common of these include omphalocele and gastroschisis,
which when grouped together occur in 1 in 2,500 live births.
 In both these defects, a portion of the gastrointestinal system herniates
beyond the anterior body wall.
 However, in omphalocele, the bowel is membrane covered, in contrast
to gastroschisis, in which the bowel protrudes through the body wall
145

Omphalocele (A) and
gastroschisis (B) in neonates.
Note that in omphalocele the
herniated bowel is contained
within a membranous sac
(part of the umbilical cord).
However, in gastroschisis the
bowel herniates through an
opening in the body wall,
typically to the right of the
umbilical cord (the umbilical
cord is clamped just proximal to
its level of transection) and is not
contained within a membranous
sac
146

Germ Layer Derivatives
•
151

Mesodermal Germ Layer
 Has three parts
 Paraxial mesoderm
 Lateral plate
o Somatic or parietal mesoderm layer
o Splanchnic or visceral mesoderm layer
 Intermediate mesoderm
152

 Paraxial Mesoderm
 Give rise to somitomeres (formed cephalocaudally since 3rd week)
which organize into somites
 First pair of somites arises at day 20 and formation continue at the
rate of three pairs per day and at the end of the fifth week, 42 to 44
pairs are present
o 4 occipital, 8 cervical, 12 thoracic, 5 lumbar, 5 sacral, and 8 to 10
coccygeal pairs
o The first occipital and the last five to seven coccygeal somites later
disappear, while the remaining somites form the axial skeleton 153

15
Paraxial Mesoderm
 The number of somites helps
to estimate age of the embryo
 Each somite forms its own
o Sclerotome - the cartilage
and bone component
o Myotome- providing the
segmental muscle
component
o Dermatome - the
segmental skin component
 Each myotome and
dermatome also has its own
nerve component.
154

The number of somite's are correlated to
approximate age in days
Approximate Age (days) Number of Somite's
20 1-4
21 4-7
22 7-10
23 10-13
24 13-17
25 17-20
26 20-23
27 23-26
28 26-29
30 34-35 155

 Lateral plate mesoderm
o Parietal will form serous membranes, peritoneal, pleural, and
pericardial cavities and secrete serous fluid
o Visceral layer will form a thin serous membrane around each organ
21-day embryo Section at the end of the 4th week
156

Ectoderm
 Surface ectoderm- epidermis, hair, nail, glands of the skin,
adenohypophysis, enamel, inner ear, lens of the eye, epithelium of the
oral and nasal cavities and the anus
 Neuroectoderm
o Neural tube- brain, spinal cord, retina, muscles of the iris,
neurohypophysis
o Neural crest- sensory and autonomic ganglia,
adrenal medulla, peripheral glial cells and pigment cells
157

Main events in specific weeks
Fourth Week
 The neural tube is formed opposite the somites and widely open
at the rostral and caudal neuropores
 By 24 days, the first two pharyngeal arches (mandibular and
hyoid) are visible
 The heart produces a large ventral prominence and pumps blood.
 By 26 days, 3 pairs of pharyngeal arches are visible and the
caudal neuropore closed
 The forebrain produces a prominent elevation of the head
158

Main events in specific weeks
Fourth Week
 Upper limb buds form by day 26 or 27 on the ventrolateral body
walls
 The otic pits and lens placodes appear
 End of the fourth week- 4th pair of pharyngeal arches and the lower
limb buds and caudal eminence form
160
Approximately 28 days

Week 5
 Bones appear during week 5 as mesenchymal condensations in the
limb buds
 Upper limbs show regional differentiation with developing hand
plates
 Mesonephric ridges indicate the site of the mesonephric kidneys
 Rapid development of the brain and facial prominences
161
32 days

Sixth Week
 Embryo show reflex response to touch
 The upper limbs begin to show regional differentiation(elbows,
handplates and digital rays develop)
 The clavicle develops by intramembranous ossification and later
develops articular cartilages
 Embryos in the sixth week show spontaneous movements, such as
twitching of the trunk and limbs
162

Sixth Week
 Development of the lower limbs 4 to 5 days later than upper
limbs
 Auricular hillocks develop -external acoustic meatus
 Retinal pigment has formed and the eye is now obvious.
 The intestines enter the extraembryonic coelom in the
proximal part of the umbilical cord, umbilical herniation
b/se of small abdominal cavity.
163

Week 7
 Loose mesenchyme between the digital rays break down and notches
appear between the digital rays in the hand plates.
 Digital rays form in the foot plate
 Ossification of the bones of the upper limbs has begun
48 days
164

Eighth Week
 Digits of hand separates
 Notches are clearly visible b/n digital
rays of the feet
 Ossification in the bones of lower limb
 Evidence of caudal eminence
disappear
 Embryo has distinct human
characteristics
 Scalp vascular plexus
 approximately 56 days
165

Estimation of embryonic age
166
Reasonable estimates of the age of the embryos can be estimated
from:
1. The day of the onset of LNMP.
2. The estimated date of fertilization ( conception ) .
3. Ultrasound assessment of the size of the chorionic sac and its
contents.
4. Measurement of the embryos :
1. Greatest length ( GL) – Straight measurement : 3rd and early 4th
week.
2. Crown rump length (CRL) – sitting height : older embryos.
3. Crown heel length (CHL) – standing height : 8 week embryos.
4. Carnegie Embryonic Staging System – International.
5. Study of the external characteristics of the embryos
1. Number of somites, pharyngeal arches
2. Size of the head
3. Formation of the limbs, face, ears, nose, eyes…

Carnegie stages
 The embryo can be classified according to age, size or
morphologic characteristics. The correlation b/n these three
criteria will allow identifying embryonic Carnegie stages
 Week 1
o Day 1, 0.1-0.15mm, stage 1, fertilization
o Day 1. stage 2, first cleavage
o Day 4,stage 3, blastocyst free in the uterine tube
o Day 5-6, stage 4, blastocyst hatches & begins implantation
 Week 2
o Day 7-12, 0.1-0.2mm, stage 5, blastocyst fully implanted
o Day 13, 0.2mm, stage 6, primary stem villi form, primitive streak
 Week 3
o Day 15-16, 0.4mm, stage 7, gastrulation, notochord process
o Day 17-18, 1-1.5mm, stage 8, neural plate &neural groove
o Day 20-21, 1.5-2.5mm, 1-3 somites, stage 9,head fold, neuromeres,
neural fold, heart beat & pump blood 167

Carnegie stages
 Week 4
o Day 22-23, 2-3.5mm, 4-12 somites, stage 10,neural tube, pairs
of pharyngeal arches, embryo curve
o Day 24-25, 2.5-4.5mm,13-20 somites, stage 11, head & tail
folding, rostral neuropore closed otic placodes, otic vesicles
o Day 26-27, 3-5mm,21-29 somites, stage 12, UL buds, caudal
neuropore closed third pair pharyngeal arches
o Day 28-30,4-6mm, 30-35 somites, stage 13,c-shaped,four pair
of pharyngeal arch, lower limb buds
 Week 5
o Day 31-32, 5-7mm, 36-44 somites, stage 14,uper limb buds
paddle
shaped, otic cups, lens pits
o Day33-36, 7-9mm, stage 15,hand plate, digital rays, cervical
sinus 168

Carnegie stages
 Week 6
o Day 37-40,stage 16 8-11mm, stage 16, foot plate, pigment in retina,
auricular hillocks
o Day 41-43, 11-14mm, stage 17, digital rays clear in hand plate, trunk
beginning to straighten, outline future auricle of external ear
 Week 7
o Day 44-46, 13-17mm,stage 18, digital rays clear in foot plate, elbow
region visible, eyelids forming, notches b/n digital rays in the hand
plate, nipple visible
o Day 47-48, 16-18mm, stage19, limb extend ventrally, midgut
herniation, trunk elongating. 169

Carnegie stages
 Week 8
o Day 49-51,18-22mm, stage 20, UL longer & bent at elbow,
finger distinct, notches b/n digital rays in foot, scalp vascular
plexus
o Day52-53, 22-24mm,stage 21, hands & feet approach, fingers
are free, toes distinct
o Day 54-55, 23-28mm, stage 22, toes free& longer, eyelids and
auricles of external ear more developed.
o Day 56, 27-31mm, stage 23, head more rounded, external
genitalia but sexless, caudal eminence disappear. 170

Fetal Period
 The period from the beginning of 9th wk to birth.
 Characteristics:-
o Differentiation of Tissues, Organ & Organ
systems
o Rapid growth of the body
o Relative slow down in growth of head.
171

Highlights of Fetal Period
Nine - twelve weeks
 Head = half CHL
 Face - broad, eyes widely separated
& move to ventral side, but eyelids
are fused, Ears lie at the side of the
head
 External genitalia appears
similar until the end of
9th wk
 At 9 weeks, liver -
erythropoiesis.
9 week fetus
172

Fetal Period
9 - 12 week cont…
 By 11th wk intestinal coils returned to
the abdomen
 By the end of 12th wk
o upper limb reach final relative length
o Primary ossification center- in (skull)
and long bones
o Erythropoiesis is by spleen
o External genitalia distinguished by
ultrasound
o Urine formation begins b/n the 9th
and 12th weeks
12 week fetus
173

Fetal Period
13-16 weeks
 14th wk coordinated limb
movement - too slight to be felt by
the mother
 Active ossification of fetal
skeleton. bones are visible by U/S
 At 14th wk - slow eye
movement occur
 By 16th wks – Ovaries contain
primordial ovarian follicles w/c
contains oogonia
 By 12-14 wks sex of external
genitalia are recognized
13th wk
174

Fetal Period
Seventeen - twenty weeks
 Growth slow down
 Quickening -felt by the mother
 Vernix caseosa: dead epidermal cells
and a fatty substance, prevent
skin from abrasions, chapping, and
hardening
 Eye brows & head hairs visible at 20
wks
 Body covered by lanugo
 Brown fat formed- produce heat
 By 18 wks - uterus is formed
o canalization of the vagina
 By 20 wks testes and ovaries
begun to descend
17-week fetus
175

Fetal Period
21- 25 week
 Substantial weight gain
 Skin wrinkled
 At 21wks- rapid eye
mov’t begin
 By 24 wks - type II
alveolar cell produce
surfactant
 Finger nail present(24wk)
 Survive if born prematurely if
given intensive care
25-week-old
177

Fetal Period
26 – 29 weeks
 At 26 wks eye lids open, lanugos & head
hair well developed.
 Toe nail become visible
 The quantity of white fat increased(3.5%)
 Spleen –erythropoiesis
 By 28 wks erythropoiesis - bone
marrow
 The lungs and pulmonary vasculature
have developed sufficiently
 Central nervous system has matured
 By 28 wks, CRL- 25 cm and weighs
approximately 1100g
30- 34 weeks
 By 30 wks eye papillary reflex
elicited
 By the end of this period skin is pink
& smooth Quantity of white fat =
8% of body weight
 Fetuses 32 wks & older usually
survive if born prematurely
178

Fetal Period
35 – 38 weeks
 Fetuses born at 35 weeks have a firm grasp
 By 36 weeks, the circumferences of the head and abdomen are
approximately equal.
 After this, the circumference of the abdomen may be greater than
that of the head.
 In full term male the testis - scrotum
 The thorax (chest) is prominent
 Breasts often protrude slightly in both sexes
 At birth -weight 3000-3,400g, CRL- 36cm & CHL -50cm
 Male fetus longer and heavier than Females
 The amount of white fat is approximately 16% of body weight
179

Fetal Period
Healthy neonates. A, At 34 weeks. B, At 38 weeks.
180

Diagram illustrating the changing proportions of the body during the fetal period. At 9
weeks, the head is approximately half the crown-heel length of the fetus. By 36 weeks,
the circumferences of the head and the abdomen are approximately equal. After this (38
weeks), the circumference of the abdomen may be greater. All stages are drawn to the
same total height
181

Estimation of fetal age
 First trimester
o Crown rump length
 In the 2nd & 3rd
trimesters
o Bi-parietal diameter
o Head circumference
o Abdominal
circumference
o Femoral length
o Foot length
182

Expected date of delivery
 The EDD of a fetus is 266 days or 38 weeks after fertilization or 280
days or 40 weeks after LNMP.
 Approximately 12% of babies are born 1 to 2 weeks after the expected
time of birth.
 The common delivery date rule (Naegele's rule) for estimating the EDD
is to count back 3 months from the first day of the LNMP and add a year
and 7 days.
o LNMP – 3 months + 1 year + 7 days
o For example, LNMP =6/5/2017, the EDD will be:
o (7+6)/(5-3)/2017 + 12 months =13 / 2 /2018
o Therefore , EDD =February 13, 2018 184

Post-maturity Syndrome
 Prolongation of pregnancy for 3 or more weeks beyond the expected
date of delivery occurs in 5% to 6% of women.
 Some infants in such pregnancies develop the post maturity syndrome
and have an increased risk of mortality.
 These fetuses have :
o Dry, parchment-like skin
o Are often overweight
o Have no lanugo
o Decreased or absent vernix caseosa
o Long nails, and
o Increased alertness. 185

The Placenta and Fetal Membranes
 Separate the fetus from the endometrium
 Area of exchange b/n the mother and uterus
 The vessels in the umbilical cord connect the placental
circulation with the fetal circulation.
 Are programmed to develop and aged faster than the fetal body
 The fetal membrane includes:
o Chorion
o Amnion
o Umbilical vesicle
o Allantois
186

Chorion
 Formed by extraembryonic somatic mesoderm , cytotrophoblast and
syncytiotrophoblast cells
 Has two parts
o Smooth chorion:- chorion laeve
 Found in abembryonic pole
 Villi are degenerate, by compression
of decidua capsularis and reduction
of blood supply
o Villous chorion, chorion frondosum (bushy chorion)
 Region with branch profusely, and enlarged villi
 Located at embryonic pole
 Form fetal portion of the placenta
187

Formation of chorionic villi
 The trophoblast differentiated in to Syncytiotrophoblast and
Cytotrophoblast
 Syncytiotrophoblast grows rapidly, becomes thick and form lacunae
 Lacunae are separated from one another by syncytium (trabecule) then
gradually communicate with each other; eventually form one large space
 The syncytiotrophoblast grows and erode the endometrium and its blood
vessels are opened up, and blood from EC fills the lacunar space
 Cells of the cytotrophoblast begin to multiply and grow into each
trabeculus, so trabeculus have a central core of cytotrophoblast covered by
syncytium and maternal blood filling lacunar space
o The trabeculus is now called a primary villus and the lacunar space is
now called the intervillous space 188

Formation of chorionic villi…ed
 The extra embryonic mesoderm, lining the inner side of the
cytotrophoblast, now invades the center of each primary villus, this
structure is called a secondary villus
 Soon there after, blood vessels can be seen in the mesoderm forming the
core of each villus, the villus is fully formed and is called tertiary villus
 The cytotrophoblast emerges through the syncytium of each villus
cytotrophoblast shell
 The villi that are first formed are attached on the fetal side to the
embryonic mesoderm and on the maternal side to the cytotrophoblastic
shell and are called anchoring villi
 Each anchoring villus consists of a stem which divides into a number of
branches = allow great surface area for exchanges b/n maternal and fetal
circulations 190

Placenta
 Fetomaternal organ that is primary site of nutrient and gas exchange
between the mother and fetus
 Has two components
o A fetal part that develops from Villous chorion
o A maternal part that is derived from Decidua basalis
 The Decidua
o Refers to the gravid endometrium
o The functional layer of the endometrium, which is shed during
parturition
o Show decidual reaction
o Decidual cells contains glycogen and lipid and produce hormones
that are nutritive for the embryo and prevent uncontrolled invasion
by the syncytiotrophoblast 192

Placenta
 The Decidua
 Has three parts:
o The decidua basalis:-
 deep to the conceptus
 Has decidual plate tightly connected to the chorion
 Forms the maternal part of the placenta
o The decidua capsularis:-
 Is the superficial part of the decidua overlying the
conceptus
 With growth of the chorionic vesicle, this layer becomes
stretched and degenerates
o The decidua parietalis:-
 Is all the remaining parts of the decidua
194

Structure of the Placenta
 The fetal part of the placenta (villous chorion) has two type of villi
o Stem villi- anchor the decidua basalis
o Freely branching villi- project into the intervillous space for
exchange
 The maternal part of the placenta is formed by the decidua basalis
o Chorionic villi invade the decidua basalis and form placental
septa that project toward the chorionic plate
o The placental septa divide the maternal part of the placenta into
irregular convex areas - cotyledons
o The lobes generally number 15 to 20
o Each cotyledon consists of two or more stem villi and their many
branch villi
o By the end of the fourth month, the decidua basalis is almost
entirely replaced by the cotyledons
196

Structure of the Placenta
 The fetal border of the placenta is covered by amniotic membrane
with umbilical cord attached to it
 The maternal border is roughed by cotyledons and covered by
cytotrophoblastic shell
 Full-term Placenta
 Is discoid with a diameter of 15 to 25 cm, 3 cm thick, and weighs
about 500 to 600 g
 At birth, it is torn from the uterine wall and, 30 minutes after the
child, is expelled
198

A full-term placenta. A. Fetal side B. Maternal side
199

Placental Membrane
 The maternal and fetal bloods do not mix with each other
 They are separated by a membrane, made up
o The endothelium of fetal blood vessels, and its BM
o Surrounding mesoderm ( CT)
o Cytotrophoblast, and its BM
o Syncytiotrophoblast
 After the 20th week, the cytotrophoblast disappear, as a result, the
placental membrane consists of three layers in most places
 Most drugs and other substances in the maternal plasma pass
through the placental membrane
200

Placental Membrane
 All interchanges takes place through this membrane and its total
surface area varies from 4-14m2
 Absorptive area is greatly increased by the presence of numerous
microvilli on the surface the syncytiotrophoblast
 Transport of molecules can be by
o Simple diffusion - O2 & CO2
o Facilitated diffusion - glucose
o Active transport - many ions
o Pinocytosis - maternal antibodies
202

Placental Circulation
 Blood flows through the lacunar spaces in the syncytiotrophoblast
begin as early as the 9th day of pregnancy
 Maternal blood in the intervillous spaces is constantly in circulation
 Blood enters the intervillous spaces is through 80 to 100 spiral
endometrial arteries
 The pressure of blood drives it right up to the chorionic plate
 Blood from the intervillous space is drained by veins that also open
into the same space
 The intervillous space of the mature placenta contains
approximately 150 mL of blood that is replenished three or four
times per minute 203

Fetal Circulation
 Poorly oxygenated blood leaves the fetus through the umbilical arteries
to the placenta.
 The umbilical veins carries oxygen-rich blood to the fetus
204

Functions of Placenta
 Exchange of Nutrients and Electrolytes :- such as amino acids, free fatty acids,
carbohydrates, and vitamins b/n fetal and maternal blood
 Exchange of Gases:- such as O2, CO2, and CO by simple diffusion
 Transmission of Maternal Antibodies - IgG
 Synthesis of several hormones:-
o Progesterone-essential for maintenance of pregnancy
o Estrogens-promote uterine growth and development of mammary gland
o hCG-used as a test to detect pregnancy in its early stage, maintains the
corpus luteum, preventing the onset of menstrual periods
o Somatomammotropy-has anti-insulin effect on the mother leading to
increase plasma level of glucose and amino acid in the maternal circulation
o Melanin spreading factors- cause discoloration of areola
206

Diagrammatic
illustration of
transfer across the
placental
membrane. The
extra-fetal tissues,
across which
transport
of substances
between the mother
and fetus occurs,
collectively
constitute the
placental
membrane. Inset,
Light micrograph
of chorionic
villus showing a
fetal capillary and
placental
membrane (arrow).
207

Abnormalities of the Placenta
 Its abnormalities could be regarding to different factors, these are:
 Abnormal shape:
o Placenta bilobata: consists of two equal lobes connected by placental
tissue
o Placenta bipartita: consists of two equal parts connected by membrane
o Placenta Succenturiata: consists of a large lobe and a smaller one
connecting together by membrane
o Placenta Circumvallata: when the peripheral edge of the placenta is
covered by a circular fold of decidua
o Placenta Fenestrata: a gap seen in the placenta covered by membranes
giving the appearance of a window.
 Abnormal position:
o Placenta previa- internal os of the uterus
 Abnormal adhesion: -
o Placenta accreta-the chorionic villi penetrates deeply in to the uterine
wall to reach the myometrium
o Placenta percreta -reaches the peritoneal coat
208

70
Placental abnormalities
209

Abnormalities of the Placenta……ed
 Abnormal in diameter
 Abnormal in weight
 Placental lesions:
o Placental infarct
o Placental tumor
 Abnormal umbilical cord attachment
o Marginal (battle-dore Placenta)
o Villamentous insertion- blood vessels are attached to
amnion, where they ramify before reaching the placenta
210

Placenta with a marginal attachment of the cord, often called a
battledore placenta because of its resemblance to the bat used in the
medieval game of battledore and shuttlecock 211

A placenta with a
velamentous
insertion of the
umbilical cord. The
cord is attached to
the membranes, not
to the
placenta.
212

Umbilical Cord
 Arise from primitive umbilical ring, at the fifth week
 The ring contains:-
o The connecting stalk, containing the allantois and the umbilical
vessels
o The yolk stalk (vitelline duct) accompanied by the vitelline vessels
o Canal connecting the intraembryonic and extraembryonic cavities
 Attachment to the placenta usually near the center of the fetal surface
 Umbilical vessels (two arteries and one vein) surrounded by the jelly
of Wharton
 Measure 1-2cm in diameter and 30-90cm in length
213

The Umbilical Vesicle (Yolk Sac)
 Is the secondary yolk sac developed by shrinking of primary yolk
sac
215

Importance of yolk sac
o Transfer of nutrients to the embryo during the second and third
weeks when the utero-placental circulation is being established
o Blood cell production from third week to sixth week
o The endoderm of the umbilical vesicle is incorporated into the
embryo
o Its endoderm, derived from epiblast, gives rise to the epithelium of
the trachea, bronchi, lungs, and digestive tract
o Origin of Primordial germ cells during 3rd week
216

Fate of yolk sac
o By 6th week, yolk stalk which was connecting yolk
sac to mid gut loop usually get detached
o By 9th wk the yolk sac shrink
o By 20 wk usually not visible
o 2-4% of adults, the proximal intra-abdominal part
may persists as an ileal diverticulum (Meckel’s
diverticulum)
217

Amniotic Fluid
 It is a clear pale, slightly alkaline fluid that fill amniotic cavity
 Its amount approximately 30 ml at 10 weeks , 450 ml at 20 weeks and 800 to
1000 ml at 37 weeks
 It is composition of water (98-99%), carbohydrates, proteins, lipids, hormones,
minerals and suspended materials like desquamated epithelial cells, meconium
and urine
 Amniotic fluid is swallowed by the fetus and absorbed by the fetus's respiratory
and digestive tracts
 Origin:-
o Fetal- active secretion from amniotic epithelium
 transudation from the fetal circulation
 fetal urine and meconium
o Maternal- transudation from the maternal circulation 218

Amniotic Fluid
 Amniotic fluid is important for the following function:
o Protects the fetus against injury
o A medium for free fetal movement
o Maintains the fetal temperature
o Source of nutrition
o Medium for fetal excretion
o Antiseptic for birth canal
o Assists in maintaining homeostasis of fluid and electrolytes
o Permits symmetric external growth of the embryo and fetus
o Permits normal fetal lung development
o Prevents adherence of the amnion to the embryo and fetus
 Polyhydramnios:- excess of amniotic fluid (1500-2000 ml)
 Oligohydramnios:- decreased amount (less than 400 ml)
219

220
Illustrations showing how the amnion
enlarges, obliterates the chorionic
cavity,& envelops the umbilical cord.
Observe that part of the umbilical vesicle is
incorporated into the embryo as the
primordial gut. Formation of the fetal part
of the placenta and degeneration of
chorionic villi are also shown.
A, At 3 weeks;
B, at 4 weeks;
C, at 10 weeks;
D, at 20 weeks.

MULTIPLE PREGNANCIES
 Is pregnancy carrying more than one fetus
o Dizygotic Twins
 Result from simultaneous shedding of two oocytes and
fertilization by different spermatozoa from same father or
different father (superfecundation)
 The twins have no more resemblance than any other brothers or
sisters
 Zygotes implant individually in the uterus, and usually each
develops its own placenta, amnion, and chorionic sac
 When the twins are implanted more closer the two placentas and
chorionic sacs fuse together , each dizygotic twin possesses red blood
cells of two different types 221

Diagrams illustrating how
dizygotic twins develop
from two zygotes.
The relationships of the
fetal membranes and
placentas are shown for
instances in which the
blastocysts implant
separately (A) and the
blastocysts implant close
together (B).
In both cases, there are
two amnions and two
chorions. The placentas
are usually fused
when they implant
close together.

MULTIPLE PREGNANCIES
 Monozygotic (Identical) twins
o Develops from a single fertilized ovum
o They result from splitting of the zygote at various stages of
development
 Two-cell stage separation
• The blastocysts implant separately, and each embryo has its
own placenta and chorionic sac and amniotic cavity resembles
dizygotic twins
 Splitting early blastocyst stage
• Most common
• The two embryos have a common placenta and a common
chorionic cavity, but separate amniotic cavities
224

Cont…
 Monozygotic (Identical) twins
 Separation at the bilaminar germ disc stage
• The twins share a single placenta and a common chorionic and
amniotic sac
• Although the twins have a common placenta, blood supply is
usually well balanced
 Division at later developmental stage
• Incomplete division of the axial area and result in Conjoined
twins
• One of the Conjoined twins may be very small (parasitic twin)
and the other may be fully developed
• Also termed as Siamese twin
225

Possible relations of fetal
membranes in monozygotic
twins.
A. Splitting occurs at the two-cell
stage (first 3 days of
development), and each embryo
has its own placenta, amniotic
cavity, and chorionic cavity.
B. Splitting of the inner cell mass
into two completely separated
groups (end of the first week) .
The two embryos have a
common placenta and a
common chorionic sac but
separate amniotic cavities.
C. Splitting of the inner cell mass
at a late stage of development
(second week).
The embryos have a common
placenta, a common amniotic
cavity, and a common chorionic
cavity.
35% 65%

227
Diagrams illustrating how some monozygotic
twins develop.
This method of development is very
uncommon. Division of the embryonic disc
results in two embryos within one amniotic sac.
A, Complete division of the embryonic disc
gives rise to twins.
B and C, Incomplete division of the disc results
in various types of conjoined twins.

3/20/2023 228
Monozygotic (Identical) twins

Multiple Pregnancies
 Other Types of Multiple Births
 Triplets may be derived from
o One zygote and be identical
o Two zygotes and consist of identical twins and a singleton
o Three zygotes and be of the same sex or of different sexes
 Although rare multiple pregnancies can occur as quadriplets,
quintiplets, sextuplets͙
230

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