GENERAL EMBRYOLOGY

OBJECTIVES
By the end of the lecture, you should be able to:
Describe the female cycles (Ovarian & Uterine).
Define gametogenesis.
Differentiate the types of gametogenesis.
Describe the process of spermatogenesis.
Describe the process of oogenesis.
 Introduction to Embryology
• Embryology:
Processes and events involved from the fertilization up to child
birth.
Why to study embryology:
Bridges the gap
B/n prenatal development and obstetrics, pediatrics,
and clinical anatomy
Develops knowledge concerning the
 Beginnings of human life and changes occurring
during prenatal development
To understand the causes of variations in human structure
Illuminates gross anatomy and explains how normal and
abnormal relations develop
Terminology
Preembryonic period: 1st week to end of 2nd week
fertilization to formation of bilaminar germ disc
Embryonic period: 3rd week to end of 8th week
formation of embryo
Fetal period: 9th week to birth growth

Perinatal stage: 26th week to 4 week after birth

DEVELOPMENTAL PERIODS
It is customary to divide human development
into prenatal (before birth) and postnatal (after
birth) periods.
The development of a human from fertilization
of an oocyte to birth is divided into two main
periods, embryonic and fetal
Stages of Embryonic Development
Early development is described in stages because of the
variable period it takes for embryos to develop certain
morphologic characteristics.
Trimester. A period of 3 months, one third of the length
of a pregnancy.
Obstetricians divide the 9-month period of gestation
into three trimesters.
The most critical stages of development occur during
the first trimester (13 weeks) when embryonic and early
fetal development is occurring
Postnatal period
• The period occurring after birth.
• Infancy
The earliest period of extrauterine life, roughly the first
year after birth.
An infant aged 1 month or younger is called a newborn
or neonate.
Transition from intrauterine to extrauterine existence
requires many critical changes, especially in the
cardiovascular and respiratory systems.
 If neonates survive the first crucial hours after birth, their
chances of living are usually good.
The body grows rapidly during infancy; total length increases
by approximately one half and weight is usually tripled.
 By 1 year of age, most children have six to eight teeth
Childhood
The period between infancy and puberty.
The primary (deciduous) teeth continue to appear and are later
replaced by the secondary (permanent) teeth.
During early childhood, there is active ossification (formation
of bone), but as the child becomes older, the rate of body
growth slows down
Puberty
The period when humans become functionally capable of
procreation through development of reproductive organs.
In females, the first signs of puberty may be after age 8;
in males puberty commonly begins at age 9.

• Adulthood
Attainment of full growth and maturity is generally
reached between the ages of 18 and 21 years.
Ossification and growth are virtually completed during
early adulthood (21 to 25 years).
REPRODUCTIVE SYSTEM MALE
REPRODUCTIVE ORGANS
FEMALE CYCLES & GAMETOGENESIS
 Female Reproductive Cycles
OVARIAN AND UTERINE CYCLES
Start at puberty
Normally continues until the
menopause.
Reproductive cycles depend upon
activities & coordination of:
Hypothalamus
Pituitary gland
Ovaries
Uterus
Uterine tubes
Vagina
Mammary glands
Gonadotrophin-releasing
hormone (GnRH) is synthesized
by neurosecretory cells in the
Hypothalamus.
• Carried to the Pituitary gland
(anterior lobe).
• It stimulates the pituitary to
release Two Hormones that act
on Ovaries (FSH & LH)
 OVARIAN CYCLE
• The ovarian cycle is under the
control of the Pituitary Gland.
• It is divided into 3 phases: (FOL)
1- Follicular, (FSH)
2- Ovulatory, (LH).
3- Luteal. (LH).
• The ovarian cortex contains
hundreds of thousands of
primordial follicles (400,000 to
500,000).
• Each consists of one primary
oocyte encircled by single layer
of flat follicular cells.
Follicular Phase
 Follicle-Stimulating Hormone .
 FUNCTIONS:
1. It stimulates the ovarian primary follicles to
develop and become mature.
2. Production of Estrogen by the follicular
cells.
Ovulatory Phase
o LH
The follicle becomes enlarged
until it gets maturity.
It produces swelling on the
surface of the ovary.
Early development of ovarian
follicle is induced by FSH.
Final stages of maturation
require LH.
LH. causes ovulation (rupture
of the mature follicle).
These Growing follicles produce estrogen which
regulates the development and functions of the
reproductive organs.
Ovulatory Phase
• Luteinizing Hormone.
FUNCTIONS:
1. It serves as the trigger for
ovulation.
2. Stimulates the mature follicles
to produce Estrogen.
3. Stimulates corpus luteum to
produce Progesterone
The remaining of the follicle is now called corpus
luteum. ruptured follicle
It secretes Progesterone and small amount of Estrogen.
These 2 hormones stimulate endometrial glands to
secrete and prepare endometrium for implantation of
fertilized Ovum (Blastocyst).

If the oocyte is fertilized the Corpus Luteum enlarges

and remains till the 4th month of pregnancy.
If the oocyte is not fertilized the corpus luteum involutes
and degenerates in 10-12 days
Cyclic changes in the endometrium of the uterus caused
by estrogen & progesterone.
Average menstrual cycle is 28 days.
Day One is the day when menstrual blood flow begins.
It varies by several days in normal women.
Ranges between 23 and 35 days in 90% of women.
It sometimes varies in the same woman.
 Gametogenesis (gamete formation)
The process of formation of gametes
Two types include:
Spermatogenesis(in male):
Formation of spermatozoa
Oogenesis (in female ):
Formation of mature oocyte
Spermatogenesis
The sequence of events by which spermatogonia are
transformed into mature sperms.
This maturation process begins at puberty.
Spermatogonia are dormant in the seminiferous tubules
of the testes during the fetal and postnatal periods.
• At puberty, they undergo a series of divisions to form
spermatogonia
The events of spermatogenesis
• There are a number of sequential stages that have been
identified during spermatogenesis
Spermatogonia(2n):stem cells: reproduce by mitosis
Primary spermatocytes: growth phase; the cells increase in
size; double their DNA content
Secondary spermatocytes: result of 1st meiotic division:
smaller than primary spermatocytes
Spermatid: result of 2nd meiotic division; smaller than
secondary spermatocytes: dense nucleus: differentiate into
sperm
Spermatozoa: fully differentiated sperm but not yet
functionally mature
 Spermiogenesis
• the series of changes resulting in the transformation of spermatids
into spermatozoa is spermiogenesis
• These changes include
1. Formation of the acrosome, which covers half of the nuclear
surface and contains enzymes to assist in penetration of the egg
and its surrounding layers during fertilization
2. Condensation of the nucleus
3. Formation of neck, middle piece, and tail
4. Shedding of most of the cytoplasm as residual bodies that are
phagocytized by Sertoli cells.
 In humans, the time required for a spermatogonium to develop
into a mature spermatozoon is approximately 74 days, and
approximately 300 million sperm cells are produced daily.
• When fully formed, spermatozoa enter the lumen of
seminiferous tubules.
• From there, they are pushed toward the epididymis by
contractile elements in the wall of the seminiferous
tubules.
• Although initially only slightly motile, spermatozoa
obtain full motility in the epididymis.
Oogenesis
Oogenesis is the sequence of events by which oogonia
are transformed into mature oocytes.
This maturation of the oocytes begins before birth and
is completed after puberty.
Oogenesis continues to menopause, which is the
permanent cessation of the menstrual cycle
Prenatal Maturation of Oocytes
During early fetal life, oogonia proliferate by mitosis, a
special type of cell division
Oogonia (primordial female sex cells) enlarge to form
primary oocytes before birth
As the primary oocytes form, connective tissue cells surround
them and form a single layer of flattened, follicular cells
The primary oocyte enclosed by this layer of cells constitutes
a primordial follicle
As the primary oocyte enlarges during puberty, the follicular
epithelial cells become cuboidal in shape and then columnar,
forming a primary follicle
The primary oocyte soon becomes surrounded by a
covering of amorphous acellular glycoprotein material,
the zona pellucida
Primary oocytes begin the first meiotic divisions before
birth, but completion of prophase does not occur until
adolescence.
The follicular cells surrounding the primary oocytes
secrete a substance, oocyte maturation inhibitor, which
keeps the meiotic process of the oocyte arrested.
Postnatal Maturation of Oocytes
Beginning during puberty, usually one follicle matures each
month and ovulation occurs, except when oral contraceptives
are used.
No primary oocytes form after birth, in contrast to the
continuous production of primary spermatocytes
The primary oocytes remain dormant in the ovarian follicles
until puberty.
As a follicle matures, the primary oocyte increases in size and
shortly before ovulation, completes the first meiotic division to
give rise to a secondary oocyte and the first polar
body(nonfunctional cell).
Unlike the corresponding stage of spermatogenesis, however,
the division of cytoplasm is unequal
• At ovulation, the nucleus of the secondary oocyte begins the
second meiotic division, but progresses only to metaphase, when
division is arrested.
• If a sperm penetrates the secondary oocyte, the second meiotic
division is completed, and most cytoplasm is again retained by
one cell, the fertilized oocyte.
There are approximately 2 million primary oocytes in the
ovaries of a newborn female, but most regress during childhood
so that by adolescence no more than 40,000 remain.
Of these, only approximately 400 become secondary oocytes
and are expelled at ovulation during the reproductive period.
 Few of these oocytes, if any, are fertilized and become mature.
The number of oocytes that ovulate is greatly reduced in women
who take oral contraceptives because the hormones in them
prevent ovulation from occurring.
Oogenesis Vs Spermatogenesis Differences

Oogenesis
Differentiation starts in IU
life.
Meiosis is completed only if
fertilization occurs
Cells may remain dormant
for years
Cytokinesis is not equal-one
main cell and one polar body
are formed
Secondary oocytes are alike-
23x
Spermatogenesis
Starts at puberty.
Both divisions are completed
before release of sperms.
Duration-64 days
Equal spermatids
Spermatocytes are of two
types-23x & 23y
1st week of human development(days 1-7)

• The following events take place during the 1st week of

development
Fertilization
Cleavage and blastocyst formation
Implantation
Fertilization
The usual site of fertilization is the ampulla of uterine tube
The fertilization process take approximately 24 hours
It is a sequence of coordinated events which include the
following stages .
1.Passage of a sperm through the corona radiata:
o For sperms to pass through the corona radiata they must have been
capacitated (removal of the glycoprotein coat and seminal plasma
proteins from the plasm membrane that overlies the acrosomal
region of the spermatozoa)
Note:
• Only capacitated sperms can pass freely through the corona
radiata
2. Penetration of the zona pellucida:
The zona is a glycoprotein shell surrounding the egg that
facilitates and maintains sperm binding and induces the
acrosome reaction
The intact acrosome of the sperm bind with a zona
glycoprotein(ZP3/zona protein3) on the zona pellucida
Release of acrosomal enzymes(acrosin) allows sperm to
penetrate the zona pellucida, thereby coming in contact
with the plasma membrane of the oocyte
As soon as the head of a sperm comes in contact with the
oocyte surface, the permeability of the zona pellucida
changes
• When a sperm comes in contact with the oocyte surface,
lysosomal enzymes are released from cortical granules lining
the plasma membrane of the oocyte
 In turn, these enzyme alter properties of the zona pellucida
to;
Prevent sperm penetration
Inactivate binding sites for spermatozoa on zona
pellucida surface
• Only one sperm seems to be able to penetrate the oocyte
3. Fusion of plasma membranes of the oocyte and sperm
The plasma membranes of sperm and oocyte come in
contact and breakdown at the site of fusion
The head and tail of sperm enter the cytoplasm of the
oocyte but its plasma membrane and mitochondrial
sheath are left behind on the oocyte surface
4. completion of the second meiotic division of oocyte and
formation of female pronucleus
Penetration of the oocyte by a sperm activates the oocyte into
completing the second meiotic division and forming a mature
oocyte and a second polar body
The nucleus of the mature ovum/oocyte is now called the
female pronucleus
Formation of the male pronucleus
• Within the cytoplasm of the oocyte, the nucleus of the sperm
enlarges to form the male pronucleus and the tail of the sperm
degenerates
Note
Since all sperm mitochondria degenerate, all mitochondria
within the zygote are of maternal origin(i.e, all mitochondrial
DNA is of maternal origin)
Morphologically, the male and female pronuclei are
indistinguishable
The oocyte now contains 2 pronuclei, each having haploid
number of chromosomes(23)
The oocyte containing two haploid pronuclei is called an ootid
5. The 2 pronuclei fuse into a single diploid aggregation of
chromosome ,ootid become zygote
The chromosomes in the zygote become arranged on a
cleavage spindle in preparation for cleavage of the zygote.
 FIRST WEEK OF DEVELOPMENT
(cleavage to implantation)
CLEAVAGE:
 It is the repeated mitotic divisions of the
zygote.
 Normally occurs in the uterine tube.
 Rapid increase in the number of the
cells.
 These smaller embryonic cells are now
called, Blastomeres.
 Cleavage begins about 30
hours after fertilization.
 Zygote divides into 2, then
4,then 8, then 16 cells.
 When there are 16 to 32
blastomeres the developing
human is called morula
 Zygote lies within the thick
zona pellucida during
cleavage.
• Mechanism:
The Morula reaches the uterine cavity by the 4th
day.
It remains free within the uterine cavity for one or
two days.
Fluid passes from uterine cavity to the Morula.
Now the Morula is transformed into Blastocyst.
BLASTOCYST
A cavity appears within the morula dividing its cells
into 2 groups
1. Outer cell layer called trophoblast.
2. Inner cell layer (mass); called Embryoblast attaché to
one of the poles of the blastocyst.
• The cavity is called blastocystic cavity or blastocele.
IMPLANTATION
• Definition:
It is the process by which the Blastocyst
penetrates the superficial (compact) layer
of the endometrium of the uterus.
 Site: (what is the normal site of
implantation?)
 IMPLANTATION
The normal site of implantation is the
posterior wall of the body of the uterus
near the fundus.
 time:
It begins about the 6th day after
fertilization.
It is completed by the 11th or 12th day.
Zona pellucida degenerates & disappears by the 5th day to
allows the blastocyst to increase in size and penetrates
the endometrium.
The embryoblast projects into the blastocystic cavity,
while the trophoblast forms the wall of the blastocyst.
CLINICALLY ORIENTED QUESTIONS
• What is the most common cause of spontaneous abortion
during the first week of development?
• Could a woman have dissimilar twins as a result of one
oocyte being fertilized by a sperm from one man and
another one being fertilized by a sperm from another
man?
By 6th day the blastocyst adheres to
the endometrium
By 7th day, Trophoblast
differentiated into 2 layers:
Syncytiotrophoblast;
• Outer multinucleated cytoplasmic
mass, with indistinct cell boundary.
Cytotrophoblast inner layer,
mitotically active.
• By 8th day the blastocyst is
superficially embedded in the
compact layer of the endometrium.
SECOND WEEK OF DEVELOPMENT
2nd week of development
Day 8
Blastocyst partially embedded in
the endometrial stroma
EXTRAUTERINE IMPLANTATION SITES

 Blastocysts sometimes implant outside the uterus.

 These implantations result in ectopic pregnancies;
95% to 98% of ectopic implantations occur in the
uterine tubes, most often in the ampulla and
isthmus
Events :
GASTRULATION
NEURULATION
Events During 3rd Week Appear To Occur In Threes

3 Germ layers of derived from bilaminar embryonic

3 New structures appear
primitive streak, notochord and allantois
3 Layer appearr in chorioniic villi
Syncytiotrophoblast
Intermediate cytotrophoblast
Inner mesodermal
 OTHER EVENTS
 Formation of primitive streak
Formation Of Neural
Plate
Tube
Crest
Formation Of Somites
Formation Of Intraembryonic Coelom
 Gastrulation
Process of formation of trilaminar germ disc
(ectoderm,mesoderm, ednderm) in embryo
Begins with formation of primitive streak on surface
epiblast
• Primitive streak formation
On 15th day, primitive streak appears that induces gastrulation
• By the end of the second week of development there is a
groove-like midline depression in the caudal end of the
bilaminar embryonic disc. This marks the appearance of the
primitive streak.
• By the beginning of week 3 the streak deepens. At the cephalic
end of the streak the primitive node develops
Elevated cranial end of primitive streak form a primitive
node (Hensen’s node or primitive knot) that surrounds a
depressed pit called primitive pit
Germ disc and primitive streak elongates craniocaudally.
A narrow depressed central area of primitive streak
called primitive groove develops.
Epiblast cells migrate toward primitive streak.
The migrating cells invaginate and detach from primitive
streak.
This migration forms a new germ layer, the intra-
embryonic mesoderm.
Invaginated cells
1. Displaces hypoblast cells to form embryonic
definitive endoderm.
2. Form a layer between endoderm and epiblast known
as intraembryonic mesoderm by the process of
epithelial to mesenchymal transformation
3. Remaining cells (non-invaginating cells) of epiblast
form definitive ectoderm.
Thus, epiblast forms all three germ layers by gastrulation
Migrating mesoderm separates ectoderm from endoderm
except at two places: Cranially at buccopharyngeal(oral)
membrane and caudally at cloacal membrane
In buccopharyngeal membrane, endodermal cells are
firmly adherent with ectodermal cells.
It is bilaminar as it is devoid of mesodermal cells
 Oropharyngeal membrane breaks down in fourth
week to form opening of oral cavity
attachment with ectoderm. This small circular
bilaminar area is called cloacal membrane.
Later, on further development, cloacal membrane
divides into anal and urogenital membranes.
Cloacal membrane disintegrates in seventh week
to form opening of anus, urethra and genital tracts.
Notochord formation
Notochord is a midline embryonic structure that
develops during third week of development from cells of
primitive node, that is, epiblast.
 Axial mesoderm (chordamesoderm) is a mesoderm that
lies along the central axis and it will give rise to
notochord.
Extent
From cranial end of primitive streak to prechordal plate.
Formation of Notochord
 Cells of primitive knot proliferate and from depression
called primitive pit.
On 17th–18th day, proliferated cells invaginat between
ectoderm up to prechordal plate to form solid cord
called notochordal process or head process.
Cavity of primitive pit extend into notochordal process to
form notochordal canal
Cells of notochordal canal fuse with endoderm.
The cells of the notochord canal disappear in a
craniocaudal direction to form a communication between
amniotic cavity (via primitive pit) and yolk sac. This
communication is called neurenteric canal.
Neurenteric canal flattens to form notochordal plate in
the roof of yolk sac.
Soon, flattening of notochordal plate reverses by
folding of notochordal plate.
Cells of notochordal plate get separated from endoderm
to form solid cord of cells called definitive notochord
 Significance of Notochord
Notochord defines axis of embryo and forms basis for
developing axial skeleton, specifically vertebral body.
It acts as primary inducer or inductor.
In humans, notochord disappears except its remnants in
adult represent nucleus pulposus of intravertebral discs
or chordomas
ALLANTOIS
Allantois or allantoenteric
diverticulum is an outpouching
of yolk sac in connecting stalk
Development and Fate
On day 16 of intrauterine life,
outpouching of yolk sac in
connecting stalk forms allantois.
On formation of the embryonic
tail fold, allantois is connected
with cloaca.
Part of allantois is absorbed in primitive urinary bladder,
whereas the remaining part of allantois forms urachus
After birth, urachus forms median umbilical ligament
In human, allantois remains small as placenta take over
its function.
Allantoic blood vessels of allantois later form umbilical
vessels
DEVELOPMENT OF CHORIONIC VILLI
Development of Fetoplacental Circulation
In second week of gestation, primary chorionic villi
(inner cytotrophoblast and outer syncytiotrophoblast)
appears.
In the beginning of the third week, mesodermal cells
penetrate in the core of primary villi to form secondary
villi.
By the end of the third week, mesodermal cells
differentiate to form capillaries. Such villi with capil-
laries are called tertiary or definitive chorionic villi.
Anchoring villus extends from chorionic plate to decidua
basalis.
FORMATION OF NEURAL TUBE/NEURULATION
 A process of formation of neural plate, neural folds and
closure of these folds to form neural tube is called
neurulation.
Under the inducing effect of the
developing notochord, the overlying
ectodermal cells thickens to form
the neural plate
On 18th day: the neural
plate invaginates to form
neural groove & neural
folds
Some neuroectodermal cells along the crest of the
neural fold differentiate as the neural crest cells.
By the end of 3rd week, the
neural folds move to the
midline and fuse to form the
neural tube

The fusion begins in the future

cervical region and then
extends both in cranial and
caudal direction
Following fusion of the
neural folds, the neural
crest cells get separated
and move laterally to form
the sensory neurons of the
spinal (dorsal root) ganglia
The neural tube separates
from the surface ectoderm, lies
in the midline, dorsal to the
notochord
Neural tube is open at both ends,
communicating freely with the
amniotic cavity.
The cranial opening, the rostral
neuropore closes at about 25th day
& the caudal neuropore closes at
about the 27th day
Closure of cranial neuropore
occurs at the 20 somite stage and
posterior neuropore at 25 somite
stage
The cranial ⅓ of the neural
tube represent the future brain
The caudal ⅔ represents the
future spinal cord
 Neural crest cells
As the neural tube forms from
the neural plate a new cell type
appears in the neural crest.
Neural crest cells appear in the
crests of the waves of the
ectoderm that are moving
towards each other
The neural tube has formed, and
neural crest cells move away
They become parts of a wide range of organs and
structures, and differentiate to form a variety of different
cell types.
For example, they will form
Much of the peripheral nervous system,
Skeletal parts of the face
Pigment cells in the skin (melanocytes).
Migration and differentiation of these cells is well
organized and an important part of the normal
development of much of the embryo.
 Migration and differentiation
The migration of neural crest cells begins in the
cranial end of the embryo shortly before the
neuropores of the neural tube close.
A cranial group of neural crest cells
migrates dorsolaterally to take part
in formation of structures of the
head and neck.
Two groups of trunk neural crest
cells migrate in different directions;
either dorsolaterally around towards
Dorsolateral migration of trunk
the midline ectoderm or ventrally neural crest cells
around the neural tube and
notochord .

Ventral migration of trunk neural

crest cells
Destinations
Differentiation of neural crest cells occurs in response to a
range of external stimuli encountered during migration.
Neural crest cells taking the dorsolateral routes towards
the ectoderm of the embryo will differentiate into the
melanocytes of the skin, for example. Some neural crest
cells in the trunk region that migrate ventrally will become
neurons of the dorsal root ganglia and sympathetic ganglia
 Clinical relevance
The most common congenital abnormalities of
neurulation are neural tube defects
As the neuropores are the last parts of the neural tube to
close, defects are most likely to occur at its cranial or
caudal ends.
Failure of the neural tube to close caudally affects the
spinal cord and the tissues that overlie it, including the
meninges, vertebral bones, muscles and skin.
The prevalence of spinal bifida, anencephaly, and encephalocele in Ethiopia was
41.09, 18.90, and 1.07 per 10 000 children, respectively
Spina bifida (from the Latin for ‘split spine’) is a condition in
which vertebrae fail to form completely.
It may manifest in different degrees of severity
Spina bifida occulta
The least severe form with a small gap in one or more
vertebrae in the region of L5–S1 often causing little or no
symptoms.
o Failure of fusion of the vertebral arch
oThe meninges do not herniate through the bony defect. This
lesion is covered by skin
oThe spinal cord and spinal nerve are normal
o An unusual tuft of hair may be present in this region of the
back
Symbtoms :
 Difficulties controlling bowel or bladder .
 Weakness and numbness in the feet
 Recurrent ulceration
Signs :
 Overlying skin lesion
 Tuft hair
Usually in the lumbar region
Spina bifida meningocoele
A failure of vertebrae to fuse that is large enough to allow
the protrusion of the meninges of the spinal cord
externally
If the spinal cord or nerve roots also protrude this is
called spina bifida with meningomyelcoele.
This may affect sensory and motor innervation at the
level of the lesion, potentially affecting bladder and anal
continence.
The neural tube may also fail to close at the cranial end,
causing abnormal brain and calvarial bone development.
The brain may be partly outside the skull (exencephaly)
or the forebrain may fail to develop entirely
(anencephaly).
 Exencephaly may precede anencephaly as the extruded
brain tissue degenerates. Anencephaly is incompatible
with life.
The incidence of neural tube defects is reduced by folic
acid supplements in the diet, but as neurulation occurs
during the third and fourth weeks it should be
considered early in pregnancy or when trying to
conceive.
What is this called ?

Meningocele
What other feature might be someone with spinal bifida
occulta have?

 Tuft of hair over region

Can a baby live with a neural tube defect?
Clinical relevance
Neural crest cells are obviously important in various areas
of embryological development, and they must migrate in a
very organised manner to complete this development
normally.
Sometimes, neural crest cells do not migrate to their
intended destinations. For example, a deficiency in the
number of neural crest cells available to form mesenchyme
in the developing face can cause cleft lip and cleft palate.
Reading assignment
• Development of Intraembryonic Coelom
• Early Development of Cardiovascular System
Organogenetic Period: 4th to 8thWeeks
 Objective
At the end of this lecture: students must be able to
understand and describe the:
Phases of Embryonic Development
Folding of the Embryo
Germ Layer Derivatives
Main developmental events of the embryo during 4th to
8th WK
Estimation of Embryonic Age
 Organogenetic Period: 4th to 8thWeeks
All major external and internal structures are
established (4th to 8th wk)
At the end of embryonic period (3rd to 8th wk):
 Main organ systems begun to develop; however,
function of most of them is minimal except CVS
Shape of embryo changes, & has a distinctly human
appearance
Most critical period, Because tissues and organs are
differentiating rapidly and, exposure of embryos to
teratogens cause major congenital anomalies
Each of the three germ layers, gives rise to a
number of specific tissues and organs
Phases Of Embryonic Development
• Human development is divided into three phases, which
to some extent are interrelated:
The first phase is growth, which involves cell division
and elaboration of cell products
The second phase is morphogenesis, the development
of shape, size, and other features of a particular organ or
part or the whole body
The third phase is differentiation, during which cells
are organized in a precise pattern of tissues and organs
that are capable of performing specialized functions.
Folding of embryo
Folding of flat trilaminar embryonic disc into cylindrical
embryo
Occurs in both median (cranial & caudal ends) and
horizontal planes (sides of embryo)
 Results from rapid growth of the embryo
 Constriction occurs at junction of embryo and umbilical
vesicle (yolk sac)
Folding of the Embryo in the Median Plane
 Folding of embryo, ventrally produces:
 Head & tail folds, result in cranial and caudal regions moving
ventrally as the embryo elongates cranially and caudally
 Median Plane : Head Fold
By beginning of 4th wk, Neural folds
in cranial region thickened to form
primordium of the brain
Initially, developing brain projects
dorsally into amniotic cavity, Later,
forebrain grows cranially beyond
oropharyngeal membrane and
overhangs the developing heart
Septum transversum, primordial
heart, pericardial coelom, and
oropharyngeal membrane move onto
the ventral surface of the embryo
Median Plane : Head Fold …

Part Endoderm of the yolk sac is incorporated into the embryo as a

foregut (primordium of pharynx, esophagus…)
The foregut lies between the brain & heart
Oropharyngeal membrane separates the foregut from the stomodeum
After head folding:
 Septum transversum lies caudal to the heart and develops into
central tendon of the diaphragm
Pericardial coelom lies ventral to the heart and cranial to the septum
transversum
Intraembryonic coelom communicates widely with extraembryonic
coelom

130
 Median Plane : Tail Fold
Folding of caudal end of the embryo results primarily from growth of
distal part of neural tube:→ Primordium of spinal cord
As embryo grows, caudal eminence (tail region) projects over
cloacal membrane:
→ Future site of anus
Part of endodermal germ layer is incorporated into the embryo as the
hindgut:
→ Primordium of descending colon
Terminal part of hindgut dilates to form cloaca: → Primordium of
urinary bladder & rectum
Before folding, primitive streak lies cranial to cloacal membrane,
after folding, it lies caudal to it

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Tail Fold

 Connecting stalk (primordium of umbilical

cord) attached to ventral surface of the
embryo
 Allantois (diverticulum of umbilical
vesicle), partially incorporated into the
embryo

132
 Folding of the Embryo: Horizontal Plane

Folding of sides of the embryo produces right and left lateral

folds:
Produced by rapidly growing spinal cord and somites
Primordia of ventrolateral wall fold toward median plane
Abdominal walls form, part of endoderm germ layer is
incorporated into the embryo as the midgut (primordium of small
intestine…)

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Folding of the Embryo: Horizontal Plane
Initially, there is a wide connection b/n midgut and umbilical
vesicle, however; after lateral folding, connection is reduced to an
omphaloenteric duct
Umbilical cord forms from connecting stalk, ventral fusion of
lateral folds reduces region of communication b/n intraembryonic
and extraembryonic coelomic cavities
Amniotic cavity expands and obliterates most of extraembryonic
coelom
Amnion forms epithelial covering of umbilical cord

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135 17
 Germ Layer Derivatives
Each of the three germ layers (ectoderm, mesoderm,
and endoderm) formed during gastrulation gives rise to
primordia of all the tissues and organs
Cells of each germ layer:
 Divide, migrate, aggregate, and differentiate to form the
various organ systems

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Germ Layer Derivatives

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 Axial skeleton,
Sclerotomes
Dermomytomes

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 Fourth Week: External Appearance
Major changes in body form occur
Embryo is almost straight
Neural tube formed opposite the somites, but widely open at
rostral and caudal neuropores (22 to 23 day)
By 24 days, First (mandibular arch)and second (hyoid arch) pairs
of pharyngeal arches visible
Embryo curved owing to head and tail folds (24- 25 day)
Heart produces large ventral prominence and pumps blood
Three pairs of pharyngeal arches are visible (by 26 days)
Rostral neuropore is closed (25 to 26 days)
Upper limb buds appear ( 26 to 27 day)
Otic pits present (primordia of internal ears)

139
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 ≈ 26 day

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By the end of 4th wk (27 to 28- 30 day):
Tail-like caudal eminence present
Fourth pair of pharyngeal arches visible
Lower limb buds appear
Forebrain produces prominent elevation of head, and folding of the
embryo has given the embryo a C-shaped curvature
Lens placodes appear(future lenses of the eyes)
Otic vesicles present
Caudal neuropore closing

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 Fifth Week
Changes in body form are minor, But
Growth of head exceeds that of other regions
 Caused mainly by rapid development of brain and facial
prominences → contacts with heart prominence
Rapidly growing second pharyngeal arch overgrows the third
and fourth arches, forming a lateral ectodermal depression on
each side-Cervical sinus
Mesonephric ridges appear (indicate site of mesonephric
kidneys), → interim excretory organs in humans

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 ≈ 32 day

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 ≈ 32 day

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Stage 14 Approx. 33th day 5 - 7 mm
1 Telencephalon
2 Mesencephalon
3 Myelencephalon

4 Ocular primordium
5 Fourth ventricle
6 Cervical sinus

7 Mesonephric cord
8 Bud of the upper extremity
9 Bud of the lower extremity

Hand plates formed; digital rays visible.

Upper limbs are paddle shaped. Lens vesicles present
Lens pits and nasal pits visible. Nasal pits prominent.
Optic cups present. Lower limbs are paddle shaped
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 Sixth Week
Upper limbs begin to show regional differentiation as elbows
and large hand plates develop
 Primordia of digits (fingers), → digital rays, begin to develop
in handplates (indicate the formation of digits)
Embryos show reflex response to touch/ spontaneous
movements (e.g., twitching of trunk and limbs)
Development of lower limbs occurs 4 to 5 days later than that
of the upper limbs

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 ≈ 42 day

 Trunk and neck have begun to straighten

 Intestines enter extraembryonic coelom in the proximal part of the umbilical
cord
 Umbilical herniation, is a normal event in the embryo
 Occurs because the abdominal cavity is too small at this age to
accommodate the rapidly growing intestine
148
 Sixth Week…
Several small swellings-auricular hillocks(forming auricle of
external ear) develop around pharyngeal groove or cleft b/ n
the first two pharyngeal arches
Groove becomes external acoustic meatus (external
auditory canal)
Retinal pigment has formed, eye is now obvious
Head is much larger relative to the trunk and is bent over
heart prominence

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 Seventh Week
Notches appear b/ n digital rays in
handplates, clearly recognizable interdigital
necrosis zones (INZ) in lower extremities
Communication b/n primordial gut and
umbilical vesicle is now reduced to
relatively slender duct, omphaloenteric
duct
By the end of 7th wk , ossification of the
bones of the upper limbs has begun
Heart musculature differentiates
Hematopoiesis begins in the liver
Head becomes rounded, raises & looks
more human
 Cloacal membrane tears

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 Eighth Week
At the beginning of 8th wk,
Digits of the hand are separated but noticeably webbed
Notches are now clearly visible b/n digital rays of the feet
Caudal eminence is still present but stubby
 Scalp vascular plexus has appeared and forms a
characteristic band around the head

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 Eighth Week….

By the end of 8th wk

All regions of limbs are apparent, digits have lengthened and
completely separated
Limb movements first occur
Ossification begins in the femur
All evidence of the caudal eminence has disappeared
Both hands and feet approach each other ventrally
Neck region is established
 Eyelids are more obvious and closing
Intestines are still in the proximal portion of the umbilical cord
Auricles of the external ears begin to assume their final shape
External sexual organs are not yet differentiated enough that
one can determine the baby's gender
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153
By the end of 8th wk

 Embryo has distinct human characteristics, however, head is still

disproportionately large, constituting almost half of the embryo
154
 Criteria for Estimating Developmental Stages in Human Embryos

NO. OF
age (days) carnegie stage SOMITES LENGTH (MM)* MAIN EXTERNAL CHARACTERISTICS
20-21 9 1-3 1.5-3.0 Flat embryonic disc. Deep neural groove and prominent neural folds.
One to three pairs of somites present.
Head fold evident.

22-23 10 4-12 1.0-3.5 Embryo straight or slightly curved.

Neural tube forming or formed opposite somites, but widely open at rostral and
caudal neuropores.
First and second pairs of pharyngeal arches visible.
24-25 11 13-20 2.5-4.5 Embryo curved owing to head and tail folds.
Rostral neuropore closing. Otic placodes present. Optic vesicles formed.

26-27 12 21-29 3.0-5.0 Upper limb buds appear. Rostral neuropore closed.
Caudal neuropore closing. Three pairs of pharyngeal arches visible.
Heart prominence distinct. Otic pits present.

28-30 13 30-35 4.0-6.0 Embryo has C-shaped curve.

Caudal neuropore closed. Upper limb buds are flipper-like.
Four pairs of pharyngeal arches visible. Lower limb buds appear.
Otic vesicles present. Lens placodes distinct.
Tail-like caudal eminence present.
31-32 14 5.0-7.0 Upper limbs are paddle shaped.
Lens pits and nasal pits visible. Optic cups present.
33-36 15 7.0-9.0 Handplates formed; digital rays visible.
Lens vesicles present. Nasal pits prominent.
Lower limbs are paddle shaped. Cervical sinuses visible.
37-40 16 8.0-11.0 Footplates formed. Pigment visible in retina.
Auricular hillocks developing.
41-43 17 11.0-14.0 Digital rays clearly visible in handplates. Auricular hillocks outline future auricle of
external ear. Trunk beginning to straighten.
6/6/2023 Cerebral vesicles prominent. 155
 NO.
AGE CARNE OF
(DAYS) GIE STAGE SOMITES LENGTH (MM)* MAIN EXTERNAL CHARACTERISTICS
44-46 18 13.0-17.0 Digital rays clearly visible in footplates.
Elbow region visible. Eyelids forming. Notches between the digital rays in the hands.
Nipples visible.

47-48 19 16.0-18.0 Limbs extend ventrally. Trunk elongating and straightening.

Midgut herniation prominent.

49-51 20 18.0-22.0 Upper limbs longer and bent at elbows. Fingers distinct but webbed. Notches between
the digital rays in the feet.
Scalp vascular plexus appears.

52-53 21 22.0-24.0 Hands and feet approach each other. Fingers are free and longer.
Toes distinct but webbed.

54-55 22 23.0-28.0 Toes free and longer.

Eyelids and auricles of external ears more developed.

56 23 27.0-31.0 Head more rounded and shows human characteristics.

External genitalia still have sexless appearance.
Distinct bulge still present in umbilical cord, caused by herniation of intestines.
Caudal eminence ("tail") has disappeared.

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 Estimation of Embryonic Age
• Crown-rump length (CRL) (sitting height)
 Correlated to Approximate Age in Weeks
Expressed in millimeters, measure from vertex of skull to
midpoint b/n apices of the buttocks

 Crown-heel length (CHL),

 Measurement from the vertex of the skull to the heel (standing
height )
CRL Approximate Age
Correlated to (mm) (weeks)
Approximate Age in 5–8 5
Weeks 10–14 6
17–22 7
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28–30 8 157
 Estimation of Embryonic Age

B & C, Crown (C)- D, Crown (C)-heel

A. Greatest (H) length
rump (R) length
length (GL)

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

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 Clinical Correlates
Ultrasound Examination of Embryos
Most women seeking obstetric care have at least one ultrasound
examination during their pregnancy for one or more of the
following reasons:
o Estimation of gestational age for confirmation of clinical dating
o Evaluation of embryonic growth when intrauterine growth
retardation is suspected
o Guidance during chorionic villus or amniotic fluid sampling
o Examination of a clinically detected pelvic mass
o Suspected ectopic pregnancy
o Possible uterine abnormality
o Detection of congenital anomalies

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 Clinical Correlates
Birth Defects
Most major organs and organ systems are formed
during 3rd to 8th wk
This period is critical for normal development, period
of organogenesis
Sensitive to insult from genetic and environmental
influences,
• Induced gross structural birth defects

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