Early Embryonic Development

Iin Novita Nurhidayati Mahmuda

Oogenesis

Gonadotropin

FSH :
Follicle maturity
Stimulate maturation of granulosa
cells which produce estrogen

Estrogen

Cause endometrium enter

proliferative phase
Thinning of cervical mucous to allow
passage of sperm
Stimulate pituitary gland to secrete
LH

LH

Causing oocyte finish meiosis I and

enter meiosis II
Stimulate production of progesteron
Cause follicular rupture and
ovulation

Ovulation

LH surge
In digestion collagen fibers
surrounding follicle
Local muscular contractions in
ovarian wall
Extrude the oocyte with some of the
cumulus oophorus which form
corona radiata

Spermatogenesis

Sperm transport

The cervix
The uterus
Isthmus uteri
The oviduct

Each of which eliminate

proportion of the original
population of sperm
To under go fertilization one
sperm must undergo
capasitation and
acrosome reaction

Fertilization

The phases of
fertilization :
Penetration of the
corona radiata
Penetration of the
zona pellucida
Fusion of the
oocyte and sperm
cell membrane

Fertilization

Sperm produces hyaluronidase to penetrate the

follicular cell layer of the corona radiata (see
diagram below). It will then interact with only
one of many receptors.
At a ZP3 receptor, the head of the sperm releases
its contents (acrosin) and burrows through the
zona pellucida and perivitelline space - the
acrosomal reaction.
Once a receptor has been activated, a series of
reactions to prevent polyspermy (the entrance of
more than one sperm).will be initiated. First, the
cell surface will be depolarized. Then, cortical
granules (lysosomes) released into the
perivitelline space will hydrolyze the other
receptors. Thus, if all functions properly, only one
sperm can enter the ovum since only one receptor
can be activated.
Fusion of the plasma membranes of the oocyte
and sperm occurs; the sperm nucleus is released
into the cytoplasm of the oocyte; the rest of the
sperm degenerates
Entrance of sperm into the oocyte causes the
secondary oocyte to complete its second meiotic
division (2 polar bodies at this point)
Male pronucleus forms and swells; pronuclei
membranes become porous
Membranes breakdown, chromosomes condense
and 46 chromatids line up on metaphase plate in
preparation for mitosis

The main result of fertilization

Restoration of diploid number

ofchromosomes
Determination of sex
Inisiation of cleavage

Masa intrauterine

1. Masa embrional
Meliputi masa pertumbuhan intrauterin sampai dengan usia kehamilan
8 minggu, di mana ovum yang dibuahi (zygote) mengadakan
pembelahan dan diferensiasi sel-sel menjadi organ-organ yang hampir
lengkap sampai terbentuk struktur yang akan berkembang menjadi
bentuk manusia. Proses pembentukan organ "dari tidak ada menjadi
ada" ini (organogenesis) pada beberapa sistem organ, misalnya
sistem sirkulasi, berlanjut terus sampai minggu ke-12, sehingga
beberapa sumber mengklasifikasikan pertumbuhan masa embrional
sampai dengan minggu ke-12 (trimester pertama kehamilan).
2. Masa fetal
Meliputi masa pertumbuhan intrauterin antara usia kehamilan minggu
ke 8-12 sampai dengan sekitar minggu ke-40 (pada kehamilan normal
/ aterm), di mana organisme yang telah memiliki struktur lengkap
tersebut melanjutkan pertumbuhan dan perkembangan yang pesat,
sampai pada keadaan yang memungkinkan untuk hidup dan berfungsi
di dunia luar (ekstrauterin).

Week I

Fertilization
Cleavage
Formation of the blastocyst
Differentiation into cytotrophoblast
and syncytiotrophoblast

Cleavage

Following mitosis, two

blastomeres form, each one
totipotent (capable of
forming its own organism)
Continuing along the
uterine tube, the zygote
divides to four, then eight
cells
Size of individual
blastomeres decreases with
progressive divisions as
zygote maintains size
A ball of 12 or more cells,
the morula, enters the
uterus around day 3

Formation of the blastocyst

Compaction: Blastomeres
clump together; the amount of
cytoplasm is reduced
Adhesion: E-cadherin gene is
expressed; these proteins
facilitate intercellular adhesion
and communication
Zona pellucida is shed, allowing
for cell growth and for uterine
fluid to infiltrate
A fluid-filled cavity
(blastocoele) forms in the
center, pushing cells to the
periphery
The outer cell layer, the
trophoblast ("tropho" - to
nourish), may have a nutritive
role as the future embryonic
part of the placenta
The inner cell mass, the future
embryo, forms as a ball of cells
on one side of the spherical
blastocyst

Differentiation into cytotrophoblast and

syncytiotrophoblast

Near the end of the first week,

the blastocyst implants in the
posterior wall of the uterus in
the presence of high hormone
levels; the blastocyst attaches
at the embryonic pole (inner
cell mass) so the embryo will
eventually be attached dorsally.
Occasionally, the blastocyst will
implant on another spot in the
uterus, potentially causing
problems (see placenta previa).
The trophoblast layer
undergoes mitosis upon contact
with the uterine wall and
differentiates into the
cytotrophoblast ("cellular"
layer) and the
syncytiotrophoblast
("multinucleated" layer).

WEEK 2

Late implantation/Uteroplacental
circulation
Bilaminar
disk, amniotic cavity and primary y
olk sac
Extra-embryonic mesoderm and
coelom
Formation of the chorion
and definitive yolk sac

Late implantation/Uteroplacental
circulation

Day 8 - The syncytiotrophoblast begins to invade the

capillaries, glands and connective tissue of the
endometrial wall of the uterus
Day 9 - Spaces known as lacunae form in the
syncytiotrophoblast; they fill with maternal blood and
glandular fluid
A closing plug covers the defect in the endometrial
epithelium caused by implantation of the blastocyst; the
epithelium will be regenerated by day 12
A network of lacunae form (spaces in the placenta filled
with maternal blood that comes into contact with fetal
villi)
Days 11-12 - primitive utero-placental circulation forms
with oxygenated maternal blood arriving via spiral
arterioles, seeping into lacunae and leaving via
endometrial venous capillaries.
Days 13-14 - primary chorionic villi develop, will
eventually become vascularized
Note the multinucleated
synctiotrophoblast and the cellular
cytotrophoblast, the bilayered
embryonic disk, and the amniotic cavity
(outlined in blue). At this point, the
syncytiotrophoblast has undergone
mitosis to erode the uterine
endometrium. The maternal capillaries
thus begin to supply the embryonic
tissues with oxygenated blood (as
demonstrated by red arrows).

Bilaminar
disk, amniotic cavity and primary yolk
sac
During implantation, a cavity
appears in the inner cell mass;
amnion forms around this amniotic
cavity; derived from amnioblasts
from the epiblast
Cells of the embryonic disc flatten
and differentiate into two layers:
-epiblast - a tall, columnar layer of
cells forming the "floor" of the
amniotic cavity (primitive ectoderm)
-hypoblast - a short, cuboidal layer
of cells forming the "roof" of the
exocoelomic cavity (primitive
endoderm)
The exocoelomic cavity and
membrane form the primary yolk
sac
Thus, bilaminar embryonic disk is
sandwiched between two "balloonlike" cavities, the amniotic cavity
and the primary yolk sac

Extra-embryonic mesoderm and

coelom

Cells derived from the

primitive ectoderm fill
the space between the
trophoblast and two
cavities
This loose connective
tissue, the
extraembryonic
mesoderm, completely
surrounds the amnion
and primary yolk sac
Fluid-filled spaces
appear in the
mesenchyme, pushing
aside the mesenchyme
to form a coelom

Formation of the chorion

and definitive yolk sac

Endodermal cells from

the hypoblast migrate to
the primary yolk sac
As the extraembryonic
coelom grows, the large
primary yolk sac pinches
off, leaving behind a
smaller, secondary yolk
sac which is "permanent"
The embryo,
surrounded by two
cavities, floats in a large
"bubble" (future
chorionic cavity)

WEEK 3

Gastrulation
: Primitive Streak and Cell Migration
s
Results of Gastrulation
: Fate of the Germ Layers
Notochord: the Primary Inducer
Neurulation: Neural Tube Formation
Neural Crest Cells and their Derivati
ves

The third week is characterized by early

morphogenic changes as the bilaminar
embryo is transformed into a trilaminar
embryo, developing the three cell lineages
that will eventually form every system.
It is also the time of early tissue and
organ differentiation of the nervous and
cardiovascular systems, as well as the
formation of future body cavities.

Gastrulation
: Primitive Streak and Cell Migrations

The primitive streak appears on the epiblast

surface, migrating caudally from the
primitive node (Hansen's node) to the cloacal
membrane where it stops; it grows by the
addition of cells at the "tail" end
Embryonic orientation established:
cranial/caudal since primitive streak migrates
caudally, right vs. left, and dorsal vs. ventral
since primitive streak occurs on dorsal side
Cells migrate from the epiblast to the middle
layer between it and the hypoblast; forming
intra-embryonic mesenchyme (loose
embryonic connective tissue)
Mesenchymal cells migrate from primitive
streak cranially to form 1)cardiogenic
mesenchyme (most cranial point), 2)the
notochordal process (also in the cranial
direction), and 3)lateral mesenchyme (to the
lateral edges where it meets with extraembryonic mesenchyme)
The length of the primitive streak will
decrease as the notochord increases and it
will eventually degenerate, so that the caudal
end of the embryo will decrease in size
If the primitive streak does not degenerate,
this undifferentiated tissue could result in a
sacro-coccygeal teratoma.

Results of Gastrulation: Origin and

Fate of the Germ Layers

All three germ layers are derived

from the epiblast.

Fate of the Germ Layers

ENDODERM : epithelial lining of respiratory and GI tract

MESODERM : cardiovascular system, reproductive/excretory
organs, smooth and striated muscle, connective tissues,
vessels, skeleton
ECTODERM : SURFACE ECTODERM - epidermis, and other
external structuresNEUROECTODERM - central and peripheral
nervous system, neural crest cells and derivatives

Epithelium is derived from all three germ layers - ex.

endoderm - epithelial lining inside viscera, mesoderm mesothelium lining outside of viscera, and ectoderm - skin
epithelium

Notochord: the Primary Inducer

The notochordal process develops by the

migration of mesenchymal cells cranially from
the primitive node, eventually stopping at the
bucco-pharyngeal membrane (a bilayer disk of
endoderm/ectoderm)
The floor of the notochordal process fuses with
the intra-embryonic endoderm of the yolk sac
The fused layers degenerate temporarily to form a
transitory communication with the yolk sac
(neurenteric canal)
The notochordal plate folds inward, to form a
rod-shaped notochord; cell proliferation occurs
cranially to caudally
As the notochord closes as a tube, it detaches
from the endoderm of the yolk sac
It is now located in the mesoderm, between the
endoderm and ectoderm
Functions of the Notochord:
1. Structure - acts as a rigid axis around which
the embryo develops
2. Skeletal - foundation upon which the
vertebral column (vertebral bodies) will form
*3. Induction - will bring about formation of the
neural tube (future nervous system)*
Fate of notochord: It will eventually break up
into section of weight-bearing intervertebral
disks, known as the nucleus pulposos (this little
structure may give rise to what is commonly
known as a "slipped disk. A tumor can occur
here, known as a chordoma, localized in the
intervertebral disk, capable of causing nerve
damage.

Neurulation: Neural Tube Formation

Neurulation includes the

formation of the neural plate
(day 18-19), neural folds (day
20-21), and the neural tube
(day 22-26); the latter will
develop into the future brain
and spinal cord
The neural plate forms as a
central strip of surface
ectoderm cells, just above the
notochord. It is induced to
become neuroectoderm
through changes in cell shape
(cuboidal to columnar) and
proliferation; the cells develop
N-CAM adhesion molecules,
disorganized filaments and
elongated tubules; this flat
layer of cells is referred to as
the neural plate

The layer of cells between the

regular surface ectoderm and
the neuroectoderm possess
characteristics of both cell
types, such as the possession
of both L-CAM (ectoderm) and
N-CAM (neuroectoderm)
adhesion molecules, and are
called neural crest cells.
At the neural plate, the cells
continue to morph into
pyramidal shaped cells with
straight neuro-tubules, neurofilaments concentrated at the
apex of the cell, connected by
desmosomes
The change in cell shape and a
decrease in cell number cause
the neuroectodermal cells to
gradually fold inward, forming
neural folds (d 20-21)

The neural tube continues to grow in this

manner, and eventually breaks free of the
surface ectoderm which will be sealed off.
Up to this point, it was supplied
continuously with amniotic fluid.
As the neural tube forms, the closing
process is critical, occurring from the cranial
to the caudal end as the anterior neuropore
closes around day 24, the posterior around
day 26. This is a critical event, as defects in
closure may result in spina bifida or other
neural tube defects. The risk of a neural tube
defect can be decreased by folic acid
supplements, a campaign led by the March
of Dimes.
The neuroepithelial cells at this stage are
bipotential, capable of forming neurons or
neuroglial cells.
Once the neural tube has closed completely,
vertebral structures develop around it, as do
meninges and finally, skin from the surface
ectoderm

Review: The notochord is of mesenchymal

origin. During formation, it is continuous with
embryonic endoderm, allowing for the neurenteric
canal between the amniotic and yolk sac cavities.
The notochord then detaches from the
endoderm to form a closed tube in the
mesoderm. On the other hand, the neural tube
originates from the ectodermal layer, when the
surface ectoderm is induced by the notochord
to form neuroectoderm. Thus, the neural tube
begins its development intercalated in the
primitive ectoderm but, like the notochord,
eventually detaches to form a closed tube.

Neural Crest Cells and their

Derivatives

As the notochord induces the transformation of surface

ectoderm to neuroectoderm, a multipotential middle cell
layer develops with characteristics of both cell types (N-CAM
and L-CAM adhesion molecules) as well as important future
roles.
These neural crest cells migrate dorsolaterally to form the
neural crest, a flattened irregular mass between the surface
ectoderm and neuroectoderm
This layer will separate into right and left portions and then
migrate to different areas (Take some time to become
familiar with these now, because they will come back in
future units!)
Note: Failure of neural crest cells to migrate will result in
anomalies such as albinism, "elephant man," or
oropharyngeal teratoma. Remember, teratomas form from
disorganized, multipotential tissues such as the primitive
streak, neural crest cells and primary germ cells.

Derivatives of Neural Crest Cells

Spinal ganglia
(prevertebral/paravertebral)
Ganglia of the autonomic nervous system
(ANS)
Ganglia of cranial nerves V, VII, IX, X
Sheaths of peripheral nerves
Meningeal coverings of brain and spinal
cord
Pigment cells (melanocytes)
Adrenal medulla
Odontoblasts of tooth
Other components of head

WEEK 4

Somite development
Intraembryonic coelom & body
cavities
Head-tail folding
Lateral folding

In week 4, the embryo undergoes major morphological

changes as it changes from a trilaminar disk-shaped
embryo to a cylindrical embryo. This is also an
important week in terms of determining placement of
future organs. Following median and horizontal folding,
many organs and body cavities will begin to form or will
be repositioned.
At the beginning of week 4, the embryo is 2.0-3.5 mm
long, straight, has 4-12 somites, and a neural tube that
has begun to close at the cranial end (rostropore).
Somites will continue to develop, increasing in number
to 20-30 during this week, the somite period of
development. They can be visualized on the surface of
the embryo and are used to estimate the age of the
embryo. They will eventually give rise to the vertebrae,
ribs, and musculature of the axial skeleton, as well as
the dermis.

Somite development

At the end of week 3, the intraembryonic mesenchyme

differentiates into three loose
aggregate pairs of mesenchyme on
each side of the neural tube
Medially, the paraxial mesoderm
differentiates into the future
dermatome (dorsal surface),
myotome (middle layer), and
sclerotome (ventral layer), forming
dermis, muscle, and connective
tissue respectively.
Moving laterally, the second
aggregate pair, called the
intermediate mesoderm, will form
the future urogenital system. Most
laterally, the lateral plate mesoderm
will develop into future body cavities
(intraembryonic coelom) and parts
of the body wall.

The paraxial mesoderm will develop into paired

cuboidal bodies, or somites (Gr. soma, body). These
will eventually develop into the bones
(sclerotome), muscles (myotome), and dermis
(dermatome) of and surrounding the axial
skeleton. Somites appear as bumps on the dorsal
surface of the embryo.
At the end of week 3, 4-12 somites are present (visible
on the dorsal surface of the embryo). By the end of
week 5, 42-44 can be counted. However, most appear
between days 20-30, giving this period the title of the
somite period of development.
Somites appear cranially to caudally, beginning at the
occipital end. They can be counted and are used to
roughly estimate the age of the embryo.

Dorsal View of an Embryo at about

22 days (8 somite stage)

Eventually, they play a

major role in
segmentation of the
embryo and the adult.
Since several somites will
disappear, the final number
is 31 pairs of somites.
Law of Original
Innervation: The
myoblasts (future muscle
cells) form concurrently
with the spinal nerves and
they migrate out from the
notochord together. This
results in the formation of
31 spinal nerves with
associated skin, muscle,
and connective tissue.

The Intra-embryonic Coelom and

Future Body Cavities

At the end of week 3, spaces in

the lateral plate and
cardiogenic mesenchyme fuse
to form a horseshoe-shaped
intra-embryonic coelom (same
process of development as the
extra-embryonic coelom).
Amniotic fluid can then
circulate in this area, as it
communicates with the extraembryonic coelom.

The curve of this horseshoe

will form the pericardial cavity
and the limbs will form the
future pleuroperitoneal cavities.

The curve of this horseshoe will form

the pericardial cavity and the limbs
will form the future pleuroperitoneal
cavities.
In the fourth week, the horseshoe
will change to a pericardial cavity,
with two symmetrical
pericardioperitoneal canals, leading
to the large peritoneal cavity.
The future body wall is formed on
the dorsal surface of the cavity of
somatic mesoderm from the lateral
plate, mesothelium, and surface
ectoderm. The future gut wall is
formed from lateral plate mesoderm,
mesothelium and endoderm on the
ventral surface of the intraembryonic coelom. During this week,
the embryo will fold laterally, so the
outer somatopleure envelops the
inner splanchnopleure.
The three body cavities (pericardial,
pleural, peritoneal) will form
definitively in the second month.

Head-Tail Folding

Due to the rapid

growth in the
median plane of
the brain, amniotic
cavity, and
somites, the
embryo elongates,
with its head and
tail ends folding
under.

At the cranial end, the

head will be folded
under, with a very
prominent forebrain.
Just cranial to it, on
the ventral side, will
lie the newly
positioned primitive
heart, pericardial
cavity, septum
transversum, and
bucco-pharyngeal
membrane.

Longitudinal section of an embryo

about to undergo head-tail folding

During this fold the future

body cavities of the intraembryonic coelom will find
their future locations and
the foregut will form from
the endoderm of the yolk
sac, resulting in a reduced
yolk sac.
At the tail end, the
endoderm of the yolk sac is
incorporated into the
embryo to form the hindgut
region. The connecting
stalk is now attached
ventrally, with the allantois
jutting into the embryo.

Lateral Folding

At the same time that head-tail

folding is occurring, lateral
folding is also occurring to form
a cylindrical embryo.
The layers of the somatopleure
surrounding the amnion grow
downwards to enclose the gut
with its splanchnopleure.
The endoderm of the yolk sac
forms the future midgut,
connected to the yolk stalk.
The folding results in the
formation of the umbilical cord,
amniotic epithelium
surrounding all the middle
layers that were enclosed
during the folding process
(extra-embryonic mesencyme
primarily, also part of the yolk
sac, allantois and extraembryonic coelom)

Resume 3rd week-8th week (the

embryonic period)

The period during which each of the

three germ layers ectoderm,
mesoderm, endoderm gives rise to
its own tissues and organ systems.
As the result of organ formation,
major feature of body form are
established