Department of Anatomy,

Faculty of Basic Medical Sciences,

College of Health Sciences,
Osun State University, Osogbo, Osun State.

ANA 203 (GENERAL EMBRYOLOGY)

(2 Units)

Dr. ADELEKE Opeyemi.

Course Description
The basic mechanisms, terminologies, principles,
problems (self-induced and abnormalities of cells and
biomolecule) are described in this course. The
methods of IVF are also briefly discussed to give
students insight into the method of assisted
reproductive technique

2
Course Objectives

• To understand what is involved in human

formation
• To understand the cells and procedures
involved in developmental procedures
• Understanding the basic mechanisms of
developmental abnormalities
• To understand the principle of teratology and
the medical/clinical implications in developing
and developed individuals
3
Cell Cycle and Cell Division

SECOND (2ND) WEEK LECTURE

 Cell Cycle and Cell Division
All cells are derived from pre-existing cells

New cells are produced for growth and to replace damaged

or old cells

The instructions for making cell parts are encoded in the

DNA, so each new cell must get a complete set of the
DNA molecules

DNA must be copied or replicated before cell division

Each new cell will then have an identical copy of the DNA

Each chromosome is composed of a single, tightly coiled

DNA molecule

Chromosomes can’t be seen when cells aren’t dividing and

are
called chromatin
DNA is tightly coiled around proteins called histones
Duplicated chromosomes are called chromatids & are held
together by the centromere
CELL CYCLE
The sequence of events by which a cell duplicates its
genome, synthesizes the other constituents of cells and
eventually divides into two daughter cells is called cell cycle.

Human cell divides once in approximately 24 hours, which

may vary in different organisms.

Cell division occurs throughout life. Cell division replaces

worn out or damaged cells, and heals wounds.

Apoptosis (programmed cell death) prevents a tumor from

occurring.

Cell division and apoptosis are two opposing processes that 6

Cell cycle is divided into two basic phases-

• Interphase– it is the phase between two successive M

phases. Interphase lasts for 95% of a cell cycle. This
phase is called resting phase but during this period the
cells prepare itself for nuclear division by cell growth.

• Interphase lasts about 20 hours in mammalian cells, but

embryonic cells complete the cell cycle in a few hours.

• M Phase (Mitotic phase)– when the actual cell division

or mitosis occurs. It starts with karyokinesis (nuclear
division) or duplication of chromosome and end with
cytokinesis or division of cell matrix (cytoplasm division).

• Mammalian cells require only about four hours to

complete the M stage.
7
The interphase phase is further divided into three stages:
G1 Stage: This is the 1st growth stage after cell division

Here, Cells mature by making more cytoplasm & organelles

and Cell carries on its normal metabolic activities

S -Stage: Here, DNA synthesis occurs and DNA replication results

in duplicated chromosomes.

G2 Stage: This is the 2nd Growth Stage after DNA has been copied

Here, All cell structures needed for division are made (e.g.
centrioles)

Both organelles & proteins are synthesized

NOTE; In adult mammals, some cells may not divide further and 8
exits the G1 phase to enter an inactive stage called Quiescent
The Mitotic (M) phase is further divided into
Four stages (PMAT):
Cytoplasm
Prophase Stage:
Nucleolus
In early prophase stage Chromatin in
nucleus condenses to form visible
chromosomes

Mitotic spindle forms from fibers in centrioles

Chromosomes

Nuclear Membrane
In late prophase stage, Nuclear membrane
& nucleolus are broken down

Chromosomes continue condensing & are

clearly visible

Spindle fibers called kinetochores attach to the

centromere of each chromosome

Spindle finishes forming between the poles of Nucleus & Nucleolus have disintegrated
9
Spindle Fibers
The mitotic spindle form from the centrioles in animal cells

Polar fibers extend from one pole of the cell to the opposite pole

Kinetochore fibers extend from the pole to the centromere of the chromosome to which
they attach


Metaphase Stage: Anaphase Stage
Chromosomes, attached to the
Occurs rapidly
kinetochore fibers, move to the
center of the cell
Sister chromatids are pulled apart to
Chromosomes are now lined up opposite poles of the cell by
at the equator kinetochore fibers

Equator of Cell

Pole of the
Cell

11
Telophase Stage:
Sister chromatids at opposite poles

Spindle disassembles

Nuclear envelope forms around each set

of sister chromatids

Nucleolus reappears

CYTOKINESIS (which means division of

the cytoplasm/cell into two, identical
halves called daughter cells) occurs.

In animal cells, cleavage furrow forms

to split cell

Chromosomes reappear as chromatin

Daughter cells of Mitosis:

Have the same number of chromosomes as each other and

as the parent cell from which they were formed

Identical to each other, but smaller than parent cell

Must grow in size to become mature cells (G1 of Interphase)

Chromosome number the same, but cells smaller

than parent cell
 Meiosis
• Meiosis- The cell division that reduces the number of chromosome into half and
results in the production of haploid daughter cells is called meiosis.

• It helps in production of haploid phase in the life cycle of sexually reproducing

organism. It involves following events.

• Two sequential cycles of nuclear and cell division called meiosis I and meiosis II but
single cycle of DNA replication.

• It involves pairing of homologous chromosome and recombination of them.

• Four haploid cells are formed at the end of meiosis II.

14
 Meiosis I
• Prophase I
 The homologous chromosomes pair and exchange DNA to form
recombinant chromosomes.
 Prophase I is divided into five phases:
• Leptotene: chromosomes start to condense.

• Zygotene: homologous chromosomes become closely associated (synapsis) to form

pairs of chromosomes (bivalents) consisting of four chromatids (tetrads).
• Pachytene: crossing over between pairs of homologous chromosomes to form
chiasma
• Diplotene: homologous chromosomes start to separate but remain attached by
chiasma.
• Diakinesis: homologous chromosomes continue to separate, and chiasmata move to
15
the ends of the chromosomes.
Metaphase I : The bivalent chromosome align at equatorial plate and
microtubules from the opposite poles of the spindle get attached to the pair of
homologous chromosomes.

Anaphase I : Homologous chromosome separate but sister chromatids

remain attached at centromere.

Telophase I: Nuclear membrane and nucleolus reappears and cytokinesis

follows.

The stage between two meiotic divisions is called interkinesis and it is short
lived that follows Prophase II.
 Meiosis II
• It is initiated immediately after cytokinesis before chromosome gets elongated.
• In prophase II, nuclear membrane disappears and chromosome becomes compact.

• At metaphase II stage, the chromosomes align at equator and microtubules attach

with kinetochores of sister chromatids.

• Anaphase II start with splitting of centromere of each chromosome to move towards

opposite poles.

• Meiosis ends with Telophase II in which two groups of chromosomes get enclosed
by nuclear membrane followed by cytokinesis to form tetrad of cells (four haploid
daughter cells).

18
• Significance of meiosis–
• Meiosis forms the gametes that are essential for sexual reproduction.
• Crossing over introduces new recombination of traits.
• Helps in maintenance of chromosome number of sexually reproducing organism.
• Provides evidence of basic relationship of organisms.

21
 • Further Reading
• © 2020 myCBSEguide | CBSE Papers & NCERT Solutions. Cell Cycle
and Cell Division class 11 Notes Biology.
PRIMORDIAL GERM CELLS –
Origin and Migration of Sex cells
Bisexually reproducing metazoans have two major lineages for two distinct lifestyle
phases, i.e. soma and germ.

Somatic cells form the body responsible for the individual life and are 'mortal‘
while Germ cells are 'immortal', because they are responsible for the species life via
procuding gametes transmitting genetic information from one generation to the next.

Primordial germ cells (PGCs) are germ-line stem cells that give rise to gametes
in vertebrates.

They originate outside the embryo very early in the development and migrate by a
well-defined route into the genital ridges.

Primordial germ cells arise from a population of pluripotent cells in the proximal
epiblast close to the extraembryonic ectoderm.
They pass through the posterior primitive streak and are found first in the posterior
part of the embryo at the base of the allantois.

They are large, round cells, which contain a high level of alkaline phosphatase
activity.

This enzymatic activity can be used to trace PGCs in the early embryo.

PGCs migrate by amoeboid movement through the hindgut and mesentery wall and
colonize the genital ridges.

The genital ridges, which give rise to the gonads, are a paired mesodermal tissue
which lies beneath the dorsal mesentery of the body.

Later, PGCs are largely confined to the developing gonads.

During their migration the PGCs proliferate and the population of about 10–100
PGCs present around day 7–8 increases to more than 20,000 in the colonized genital
ridges around day 14 of development.
Genital ridges seem to release intrinsic factors which stimulate the proliferation
of PGCs and which act as chemoattractants for PGCs in vitro.

At day 12.5 differences between male and female genital ridges become
apparent and male and female germ cells embark on their specific
developmental programmes.

The SRY (Sex-determining Region of the Y chromosome) directs male

development in mammals by inducing the somatic cells of the gonadal ridge to
develop into a testis, rather than an ovary.

Sry is expressed in a small group of somatic cells of the gonads and influences
these cells to become Sertoli cells (supporting cells in testis).

 In the absence of the Sry gene, primordial germ cells differentiate into eggs.

Retinoic acid (RA) is an important factor that causes differentiation of

primordial germ cells. In males, the mesonephros releases retinoic acid.
 SEXUAL CYCLES –
Puberty, Ovarian and uterine cycles,
ovulation, menstruation

FOURTH (4TH) WEEK

LECTURE
 PUBERTY

• Puberty is the period during which growing boys or girls undergo the
process of sexual maturation and achievement of fertility.

• The time when puberty begins varies greatly among individuals;

however, puberty usually occurs in girls between the ages of 10
and 14 and between the ages of 12 and 16 in boys.

• Both genetic and environmental factors are involved in the timing

of puberty.

• Precocious puberty is puberty that occurs earlier than normal due

to early release/rise of sex hormones from the hypothalamus.

• Girls are more likely than boys to have precocious puberty.

 PUBERTY
• Puberty may also be accompanied by emotional and mood changes.

• Body fat and/or body composition may play a role in regulating the
onset of puberty.

• Puberty is associated with the development of secondary sex

characteristics and rapid growth.
• SECONDARY SEX CHARACTERISTCS IN MALE
• Enlargement of the testes (testicles) and penis/ Erection
• Presence of pubic hair, axillary hair, and facial hair
• Foreskin retraction
• Voice change (Deepen voice) and appearance of Adam's apple
• Male musculature and body shape
• Body odor and acne
 • SECONDARY SEX CHARACTERISTCS IN FEMALE
• Breast development (Thelarche)
• Initiation of menstrual periods (First menstrual bleeding Menarche)
• Increasing in sweat production
• Body odor and acne
• Lowering of the pitch of voice,
• Rapid height acquisition ("growth spurt")
• Presence of pubic hair, axillary hair
• Body shape, fat distribution, and body composition
• Increase in size and strength of muscles.
 OVARIAN CYCLE
• Ovarian cycle can be define as the series of changes in the ovary
during which the follicle matures, the ovum is shed and corpus
luteum formed.

• Monthly sexual cycles undergo by female at puberty are controlled

by the Hypothalamus-Pituitary-Gonadal pathways.

• Hypothalamus-Pituitary-Gonadal pathways
• Hypothalumus produces Gonadotropin-releasing hormone
(GnRH).

• GnRH acts on cells of the anterior pituitary gland, which make

anterior pituitary to secrete gonadotropins (follicle-stimulating
hormone (FSH) and luteinizing hormone (LH)).

• These hormones, (follicle-stimulating hormone (FSH) and

 OVARIAN CYCLE
• At the beginning of each ovarian cycle, FSH stimulate ovary to
produce 15 to 20 primary follicles.

• NOTE: (FSH is not necessary during the maturation of primordial

follicles to the primary follicle stage, but very essential for the
maturation of primary follicles to Secondary follicle, without it Primary
follicle will die and become atretic)

• Out of these 15-20 primary follicles; only one primary follicle reaches
full maturity, and only one oocyte is discharged. The other follicles
degenerate and become atretic.

•These 15 to 20 follicles passes through three stages: 1) primary or

preantral; 2) secondary (antral, vesicular or Graafian); and 3)
Preovulatory.

•
 OVARIAN CYCLE (Maturation of Follicle).
•As the primary oocyte begins to grow, surrounding follicular cells
change from flat to cuboidal and proliferate to produce a stratified
epithelium of granulosa cells, thus primordial follicle change to
primary follicle.

•Granulosa cells rest on a basement membrane called theca

folliculi.

•Granulosa cells and the oocyte secrete a layer of glycoproteins on

the surface of the oocyte that form zona pellucida.

•As follicles continue to grow, cells of the theca folliculi organize into
theca interna (i.e. an inner layer of secretory cells) and the theca
externa (i.e. an outer fibrous capsule).

• As development continues, fluid-filled spaces appear between

 OVARIAN CYCLE (Maturation of Follicle).
•At this stage, Granulosa cells surrounding the secondary oocyte are
now called cumulus oophorus

•When secondary follicle is mature (≥25mm), a surge in Luteinizing

Hormone induces the preovulatory growth phase.

•At preovulatory growth phase, meiosis I is completed, resulting in

formation of two daughter cells of unequal size, each with 23 double
structured chromosomes.

•The secondary oocyte, receives most of the cytoplasm while the

first polar body receives none.

•The cell then enters meiosis II but arrests in metaphase

approximately 3 hours before ovulation.
 ROLES OF STEROID HORMONES IN OVARIAN CYCLE

1. Folicular Stimulating Hormone (FSH)

 FSH is very essential for the maturation of primary follicles to
secondary follicle.
 FSH stimulates maturation of follicular (granulosa) cells
surrounding the oocyte.

NOTE; Follicular cells proliferation are also being mediated by growth

differentiation factor-9 (GDF-9).
• Few days to the maturation of secondary follicles, follicular and
thecal cells produce Estrogen.

2. Estrogen produced
 Cause the uterine endometrium to enter the follicular or proliferative
phase
 ROLES OF STEROID HORMONES IN OVARIAN CYCLE
3. Leutinizing Hormone (LH)
o Help the secondary follicle to enter the preovulatory stage
o Causing the primary oocyte to complete meiosis I, and to enter
meiosis II.
o Stimulation and production of progesterone by follicular stromal cells
o Causes follicular rupture and ovulation.
 OVULATION
• Ovulation can be define has the release of secondary oocyte (eggs
or ova) from the ovaries.

• As the secondary oocyte is arrested in metaphase approximately 3

hours before ovulation, the surface of the ovary begins to bulge
locally, and at the apex, an avascular spot called (the stigma)
appears.

• The high concentration of LH increases collagenase activity,

resulting in digestion of collagen fibers surrounding the follicle.

• Prostaglandin levels also increase in response to the LH surge and

cause local muscular contractions in the ovarian wall.

• Those contractions extrude the oocyte and its surrounding granulosa

cells from the region of the cumulus oophorus.
 OVULATION
• Some of the cumulus oophorus cells then rearrange themselves
around the zona pellucida to form the corona radiata

• After ovulation, remaining granulosa cells in the wall of the

ruptured follicle, together with cells from the theca interna, are
vascularized by surrounding vessels.

• Under the influence of LH, these (remaining granulosa and theca

cells) develop to a yellowish pigment and change into lutean cells,
which form the corpus luteum and secrete the hormone
progesterone
 UTERINE/ MENSTRUAL CYCLE
• From puberty till menopause, the endometrium undergoes changes in
a cycle of approximately 28 days under hormonal control by the ovary
(Menstrual cycle).

• The wall of the uterus consists of three layers:

1. Endometrium (mucosa lining the inside wall, it

consists of Superficial compact layer,
Intermediate spongy layer and Thin basal layer).

2. Myometrium (a thick layer of smooth muscle);

3. Perimetrium (the peritoneal covering lining the outside

wall)
 UTERINE/ MENSTRUAL CYCLE
• During menstrual cycle, the uterine endometrium passes through
three stages:

1. The menstrual phase:

• Menstrual phase occur if fertilization does not take place.

• Menstruation is the beginning of the endometrial/uterine cycle, when

the unneeded uterine tissue sheds (i.e. shedding of compact and
spongy layers of the endometrium).

• If the oocyte is not fertilized, venules and sinusoidal spaces in the

endometrium gradually become packed with blood cells, and an
extensive diapedesis of blood into the tissue is seen.

• When the menstrual phase begins, blood escapes from superficial

arteries, and small pieces of stroma and glands break away.
 UTERINE/ MENSTRUAL CYCLE Contd…
• During the following 3 or 4 days, the compact and spongy layers are
expelled from the uterus, and the basal layer is the only part of the
endometrium that is retained.

2. The follicular or proliferative phase

• Begins at the end of the menstrual phase, which is the period of
tissue regeneration

• Proliferative phase is influence by estrogen hormone and parallels

growth of the ovarian follicles at the same time.

• The basal layer which is the only layer retained after menstrual phase
will be supply by its own arteries (basal arteries).

• During proliferative phase, the basal layer helps to regenerative

shed compact and spongy layers and in the rebuilding of glands and
 UTERINE/ MENSTRUAL CYCLE Contd…
• Proliferative phase terminates after ovulation.

3. The secretory or progestational phase:

• Begins approximately 2 to 3 days after ovulation in response to
progesterone produced by the corpus luteum.

• During Secretory/progestational phase, the arteries and glands

supplying the tissue regenerate.

• NOTE; If fertilization occur, the endometrium assists in

implantation and contributes to formation of the placenta.

• At the time of implantation, the mucosa of the uterus enter secretory

Phase again

• During this time uterine glands and arteries become coiled and the
 • TUTORIAL QUESTIONS
1. Gonadotropin releasing hormone, Follicle stimulating hormone
and Luteinizing hormone are very essential in controlling cyclic
changes in the ovary. Explain

2. Enumerate the secondary sex characters in female

3. What do you understand by ovarian and endometrial cycle

4. Highlight the features of follicular phase

 • REFERENCES
• Archer, D.F., Zeleznik A.J., Rockette H.E (1988): Ovarian follicular
maturation in women: Reversal of estrogen inhibited ovarian
folliculogenesis by human gonadotropin. Fertil Steril 50:555.

• Sadler, T. W and Montana, T.B (2006). Langman’s Medical Embryology.

9th edition.
SECOND WEEK OF DEVELOPMENT

SIXTH (6TH) WEEK LECTURE

 EVENTS THAT OCCUR AT THE SECOND WEEK OF DEVELOPMENT

• Second week development is also known as week of twos i.e. week of Bilaminar germ disc formation

• AT THE EIGHTH DAY OF DEVELOPMENT, the blastocyst is partially embedded in the endometrial
stroma.

• Blastocyst embedment occur at the embryoblast region

• The trophoblast differentiated into two layers:

• (1) an inner layer of mononucleated cells with distinct cell boundaries (the
cytotrophoblast), and

• (2) an outer multinucleated zone without distinct cell boundaries (the syncytiotrophoblast)

• Cytotrophoblast undergo mitotic division but syncytiotrophoblast does not.

• Thus, cells in the cytotrophoblast divide and migrate into the syncytiotrophoblast, where they fuse
and lose their individual cell membranes.

• Cells of the inner cell mass (embryoblast) also differentiate into two flat disc shape layers:
 • EVENTS THAT OCCUR AT THE SECOND WEEK OF DEVELOPMENT Contd…

• At this time, a small cavity appears within the epiblast, the cavity enlarges to become the amniotic
cavity.

• Epiblast cells adjacent to the cytotrophoblast are called amnioblasts

• The endometrial stroma adjacent to the implantation site is edematous and highly vascular.

• The large, tortuous uterine glands secrete abundant glycogen and mucus.

• AT DAY NINE (9) OF DEVELOPMENT, the blastocyst is more deeply embedded in the endometrium,
and the penetration defect in the surface epithelium is closed by a fibrin coagulum.

• Vacuoles appear on the syncytiotrophoblast especially at the embryonic pole, sooner these vacuoles
fuse to form large lacunae, and this phase of trophoblast development is thus known as the
syncytial lacunae stage.

• At the abembryonic pole, flattened cells probably originating from the hypoblast form a thin
membrane (The exocoelomic (Heuser’s) membrane).

• Heuser’s membrane lines the inner surface of the cytotrophoblast and this membrane together with
 • EVENTS THAT OCCUR AT THE SECOND WEEK OF DEVELOPMENT Contd…

• BY THE 11TH TO 12TH DAY OF DEVELOPMENT, the blastocyst is completely embedded in the
endometrial stroma.

• The trophoblast lacunar spaces (syncytial lacunae) at this stage form an intercommunicating
network. This network is particularly seen at the embryonic pole while the abembryonic pole still
consists mainly of cytotrophoblastic cells.

• Concurrently, cells of the syncytiotrophoblast penetrate deeper into the stroma and erode the
endothelial lining of the maternal capillaries.

• These capillaries, which are congested and dilated, are known as sinusoids.

• The syncytial lacunae become continuous with the sinusoids, thus; maternal blood enters the
lacunar system.

• As the trophoblast continues to erode more and more sinusoids, maternal blood begins to flow
through the trophoblastic system, establishing the uteroplacental circulation.

• Around this same time, a new population of cells derived from yolk sac cells, form a fine, loose
 • EVENTS THAT OCCUR AT THE SECOND WEEK OF DEVELOPMENT Contd…

• Soon, large cavities develop in the extraembryonic mesoderm, and when these become confluent,
they form a new space known as the extraembryonic coelom.

• This space surrounds the primitive yolk sac and amniotic cavity except where the germ disc is
connected to the trophoblast by the connecting stalk.

• The extraembryonic mesoderm lining the cytotrophoblast and amnion is called the extraembryonic
somatopleuric mesoderm; the lining covering the yolk sac is known as the extraembryonic
splanchnopleuric mesoderm.

• Around day 12, Endometrium undergo decidua reaction in which Cells of the endometrium become
polyhedral and loaded with glycogen and lipids; moreover, intercellular spaces are filled with
extravasate, and the tissue is edematous.

• BY THE 13TH DAY OF DEVELOPMENT, the surface defect in the endometrium has usually healed.

• NOTE; Sometimes, bleeding occurs at the implantation site as a result of increased blood flow into
the lacunar spaces and because this bleeding occurs near the 28th day of the menstrual cycle, it may
 • EVENTS THAT OCCUR AT THE SECOND WEEK OF DEVELOPMENT Contd…

• At day 13, trophoblast is seen with numerous villous structures. These villous structures was as a result of
cytotrophoblast cells proliferating locally and penetrate into the syncytiotrophoblast, forming cellular
columns surrounded by syncytium.

• Thus, Cellular columns with the syncytial covering are known as primary villi.

• At day 13, the hypoblast produces additional cells that migrate along the inside of the exocoelomic
membrane.

• These cells proliferate and gradually form a new cavity within the exocoelomic cavity.

• This new cavity is known as the secondary yolk sac or definitive yolk sac.

• During secondary yolk sac formation, large portions of the exocoelomic cavity are pinched off.

• These pinched off portions are represented by exocoelomic cysts, which are often found in the
extraembryonic coelom or chorionic cavity.

• Meanwhile, the extraembryonic coelom expands and forms a large cavity, the chorionic cavity.

• The extraembryonic mesoderm lining the inside of the cytotrophoblast is then known as the chorionic
THIRD WEEK OF DEVELOPMENT

SIXTH (6TH) WEEK LECTURE

 EVENTS THAT OCCUR AT THE THIRD WEEK OF DEVELOPMENT

• Third week of development is known as week of three’s

• Gastrulation is the first noticeable event that occur @ 3rd week

• GASTRULATION is the process that establishes all three germ layers (ectoderm, mesoderm, and
endoderm) in the embryo.

• Gastrulation begins with formation of the primitive streak (narrow groove with slightly bulging
regions) on the surface of the epiblast.

• The cephalic end of the streak, the primitive node, consists of a slightly elevated area surrounding the
small primitive pit.

• Cells of the epiblast migrate toward the primitive streak, Upon arrival in the region of the streak, they
become flask-shaped, detach from the epiblast, and slip beneath it (The process called
Invagination).

• Once the cells have invaginated, some displace the hypoblast to form endoderm, and others come
to lie between the epiblast and newly created endoderm to form mesoderm.
 EVENTS THAT OCCUR AT THE THIRD WEEK OF DEVELOPMENT Contd…

• At 3rd week Notochord formation which is the basis of axial skeleton also begins

• Notochord formation start when Prenotochordal cells invaginating in the primitive pit move
towards the cephalic region of the embryo until they reach the prechordal plate.

• These prenotochordal cells become intercalated in the hypoblast so that the midline of the embryo
consists of two cell layers that form the notochordal plate.

• As the hypoblast is replaced by endoderm cells moving in at the streak, cells of the notochordal plate
proliferate and detach from the endoderm.

• They then form a solid cord of cells, the definitive notochord which underlies the neural tube and
serves as the basis for the axial skeleton.

• Because elongation of the notochord is a dynamic process, the cranial end forms first, and caudal
regions are added as the primitive streak assumes a more caudal position.

• The notochord and prenotochordal cells extend cranially to the prechordal plate and caudally to the
primitive pit.
 EVENTS THAT OCCUR AT THE THIRD WEEK OF DEVELOPMENT Contd…

• At the point where the pit forms an indentation in the epiblast, the neurenteric canal temporarily
connects the amniotic and yolk sac cavities.

• The cloacal membrane is formed at the caudal end of the embryonic disc.

• When the cloacal membrane appears, the posterior wall of the yolk sac forms a small diverticulum
that extends into the connecting stalk.

• This diverticulum (the allantoenteric diverticulum, or allantois), appears around the 16th day of
development.

• In humans Allantois remains rudimentary but may be involved in abnormalities of bladder

development
 EVENTS THAT OCCUR AT THE THIRD WEEK OF DEVELOPMENT Contd…

• Further Development of the Trophoblast

• By the beginning of the third week, the trophoblast is characterized by primary villi that consist of a
cytotrophoblastic core covered by a syncytial layer.

• During further development, mesodermal cells penetrate the core of primary villi and grow toward
the decidua. Thus, the newly formed structure is known as a secondary villus.

• By the end of the third week, mesodermal cells in the core of the villus begin to differentiate into
blood cells and small blood vessels, forming the villous capillary system and the villus at this stage is
now known as a tertiary villus or definitive placental villus.

• Capillaries in tertiary villi make contact with capillaries developing in mesoderm of the chorionic plate
and in the connecting stalk.

• These vessels, in turn, establish contact with the intraembryonic circulatory system, connecting the
placenta and the embryo.

• Hence, when the heart begins to beat in the fourth week of development, the villous system is ready
 EVENTS THAT OCCUR AT THE THIRD WEEK OF DEVELOPMENT Contd…

• Meanwhile, cytotrophoblastic cells in the villi penetrate progressively into the overlying syncytium
until they reach the maternal endometrium.

• Here they establish contact with similar extensions of neighboring villous stems, forming a thin outer
cytotrophoblast shell.

• This shell gradually surrounds the trophoblast entirely and attaches the chorionic sac firmly to the
maternal endometrial tissue.

• Villi that extend from the chorionic plate to the decidua basalis are called stem or anchoring
villi.

• Those that branch from the sides of stem villi are free (terminal) villi, through which exchange of
nutrients and other factors will occur.

• The chorionic cavity, meanwhile, becomes larger, and by the 19th or 20 th day, the embryo is attached
to its trophoblastic shell by a narrow connecting stalk.

• The connecting stalk later develops into the umbilical cord, which forms the connection between
 EVENTS THAT OCCUR AT THE THIRD WEEK OF DEVELOPMENT Contd…
Establishment of the Body Axes/ Genes that control 3 week development

• Establishment of the body axes (anteroposterior, dorsoventral, and left-right), takes place before and
during the period of gastrulation.

• Cells in the hypoblast (endoderm) at the cephalic margin of the disc form the anterior visceral
endoderm that expresses head-forming genes (OTX2, LIM1, and HESX1 and the secreted factor
Cerberus).

• Nodal, a member of the transforming growth factor β (TGF-β) family of genes, is then activated and
initiates and maintains the integrity of the node and streak.

• Bone morphogenetic protein-4 (BMP-4), in the presence of fibroblast growth factor (FGF),
ventralizes mesoderm during gastrulation so that it forms intermediate and lateral plate mesoderm.

• Chordin, noggin, and follistatin antagonize BMP-4 activity and dorsalize mesoderm to form the
notochord and somitomeres in the head region.

• Formation of these structures in more caudal regions is regulated by the Brachyury (T) gene.

• Left-right asymmetry is regulated by a cascade of genes; FGF-8, secreted by cells in the node and
 ASSIGNMENT
What are the Congenital anomalies that result during Fertilization and Pre-
embryonic stage?
• TUTORIAL QUESTIONS
1. Differentiate between cytotrophoblast and syncytotrophoblast

2. Briefly explain uteroplacental circulation

3. Highlight the genes that control third week of development

4. The second week of development is known as the week of twos. Formation

of what structures support this statement?

5. What do you understand by gastrulation

6. Highlight the events that occur at day 8 and 9 of embryonic development

 • REFERENCES
• Aplin JD (1991). Implantation, trophoblast differentiation and
hemochorial placentation: mechanistic evidence in vivo and in vitro. J
Cell Sci 99:681.

• Bianchi DW, Wilkins-Haug LE, Enders AC, Hay ED (1993). Origin of

extraembryonic mesoderm in experimental animals: relevance to
chorionic mosaicism in humans. Am J Med Genet 46:542.

• Sadler, T. W and Montana, T.B (2006). Langman’s Medical Embryology.

9th edition.