General embryology for students reading part I (2).pptx

Introduction to Human Embryology
 Embryology :- the study of embryos, generally
prenatal dev’t.
The study of the origin and development of an organism.
Developmental anatomy is the field of embryology
concerned with the changes that cells, tissues, organs,
and the body as a whole undergo from a germ cell of each
parent to the resulting adult.
Prenatal development is more rapid than postnatal
development and results in more striking changes.

Human development is a continuous process that begins when
an oocyte (ovum) from a female is fertilized by a sperm
(spermatozoon) from a male.
Cell division, cell migration, programmed cell death,
differentiation, growth, and cell rearrangement transform the
fertilized oocyte, a highly specialized, totipotent cell, a zygote,
into a multicellular human being.

✽ Development
☞ Growth (↑ in mass of tissues)
☞ Differentiation (↑ in complexity)
✽ Development does not stop at birth. Important changes, in
addition to growth, occur after birth.
✽ Divided into:
☞ Prenatal period ►pre & embryonic period
► fetal period
☞ Postnatal period (after birth) ✹ neonatal period and Infancy
✹ childhood
✹ adolescence
✹ adulthood

 Illuminates gross anatomy and explains how normal and
abnormal relations develop.
 bridges the gap between prenatal development
&obstetrics and pediatrics.
 Develops knowledge concerning the beginnings of
human life and the changes occurring during prenatal
development.
 helps to understand the causes of variations in human
structure.
SIGNIFICANCE OF EMBRYOLOGY

Internal genitalia( uterus, uterine tube ,ovaries and
vagina ).
External genitalia ( clitoris, labia majora ,labia minora
,vestibule ,mons pubis)
Female reproductive structures
Includes :-

Uterus
Hollow thick walled, pear shaped muscular organ.
Size ; 7-8 cm length , 2-3 cm thick in non pregnant
Parts:- body, cervix &isthmus
Wall :- perimetrium myometrium & endometrium

Layers of Endometrium :- 4-5 mm thick
During secretory phase of menstrual cycle three layer of
endometrium can be identified microscopically . functional
layer- shade during menstruation
thin compact layer:-densely packed CT
thick spongy layer:-edematous CT.
Basal layer:- is not sloughed off during
menstruation

Female reproductive cycle (sexual cycles
Begin at puberty ,prepare reproductive organ for pregnancy.
It involves hypothalamus , pituitary gland ,ovaries, uterus,
uterine tubes, vagina, and mammary glands
Hypothalamus--- GnRH--- pituitary --- LH & FSH.
FSH :-dev’t of ovarian follicle & estrogen production
LH:-ovulation & progesterone production.
Ovarian Cycle :-cyclic change on the ovary, by LH & FSH
-development of follicle
-ovulation
-dev’t of corpus luteum

1. Follicular dev’t
It is characterized by :-
Growth & differentiation of primary oocyte.
Proliferation of follicular cells
Formation of zona pellucida/helps to prevent
Poly spermy and premature implantation
Development of the theca folliculi
2. Ovulation
-FSH & LH- ovarian follicle , sudden growth burst
,swelling and stigma.
-LH surge - follicular rupture &
secondary oocyte expel , meiosis I end ,meiosis II
started.

The principle mechanism leading to expulsion
of oocyte is:
A.Raised intrafollicular pressure
B.Contraction of smooth muscles in theca externa
C. Enzymatic/collagenaze digestion of follicular wall
D. Increased LH production from pituitary gland
3. Corpus luteum
Glandular structure
Formed by follicular cell & theca folliculi
Produce some estrogen & mainly progesterone
Type :- of pregnancy
:- of menstruation

Corpus luteum of pregnancy:-
formed if ovum is fertilized
It enlarge and increase its hormone production
human Chorionic Gonadotropin prevent its
degeneration
Functionality - upto 20weeks of pregnancy
Corpus luteum of menstruation
formed if the ovum is not fertilized
Degenerate 10-12 days after ovulation
Subsequently changed to corpus albicans

1 Oocyte
2 Pellucid zone
3 Stratum granulosum
4 Theca interna
5 Theca externa
6 Antral follicle
7 Cumulus oophorus
(Granulosa cells, together
with the oocyte)
8 Basal lamina between
theca and stratum
granulosum

Menstrual ( endometrial )cycle
A cyclic changes in the endometrium
Produced by estrogen and progesterone
Time during w/c – oocyte matures, ovulated, and enters the
uterine tube
Phases of the Menstrual Cycle

Phases of the Menstrual Cycle
1. Menstrual phase
-80ml of blood flows
-functional layer sloughed off
2. Proliferative phase/estrogenic/follicular
-thickness of functional layer
-by increased estrogen
-follicles proliferate
3. Secretary phase/luteal/progestetional
-progestrone stimulates uterus to secrete glycogen
-spiral arteries grow,enlarge
-if ova is not fertilizzed there will be intermitent
contraction of the uterus. The ova come to uterus.
4. Ischemic phase
-corpus luteum degenerate
-spiral arteries bacame constricted
-marked shrinkage of endometrium.

• Includes
scrotum,testes,
spermatic ducts,
sex glands and
penus.
• Work together to
produce sperm
and semen as well
as to deliver it out
of body and into
the vagina.
Male reproductive system

THE BEGINNING OF HUMAN DEVELOPMENT
Gametogenesis & anatomy of female reproductive trac
 Conversion of primordial Germ Cells into Male and Female
Gametes.
spermatogenesis and oogenesis
The sequence of gametogenesis is the same, but the timing
of events during meiosis differs in the two sexes. Involve
mitosis , meiosis and cytodifferentiation.
prepares these sex cells for fertilization.

Gametes are derived from primordial germ cells
(PGCs) that are formed in the epiblast during 2nd week &
that move to the wall of yalk sac .
During 4rth week these cells begin to migrate toward
the developing gonads where they arrive by 5th week.
mitotic division Increase their number during their
migration.
When they arrive in the gonad ,in preparation for
fertilization ,germ cells undergo gametogenesis which
includes meiosis to decrease chromosome no.by meiosis
&cytodifferentiation to complete their maturation.
Phases of Gametogenesis:-

Meiosis
Special type of cell division that takes place in germ cells only in
the gonads to generate male and female gametes.
Reduce chromosome number by half to haploid.
Require two cell divisions meiosis I and meiosis II
Meiosis I-
Prophase I :- chromosomes condense
 Homologous chromosomes lie side by side forming tetrad
or bivalent.
Crossing over ,physical exchange of b/n chromosome
segments of nonsister chromatid occurs.
sister chromatids of homolog.chrom. attach to spindle fibers
by the kinotochores.
Metaphase I:-homologous pairs align at the equator randomly

Anaphase I :-the homologous chr.separate & move towards
opposite poles.
 Telophase I:-chromosome decondense &nuclear
envelope reforms.
cytokinesis separate the cytoplasm &the two daughter
cells form by cleavage furrow.

Meiosis II
Prophase II:- no DNA replication
-chromosome condense
-spindle fibers form.
Metaphase II :-chromosome align at the equator.
Anaphase II & telophase II:-single chromatid
chromosome is distributed to each daughter cell.
Cytokinesis:-cell divide & produce 4 Spermatids in Male
-1 definitive oocyte & 3 polar bodies in Female
- all contain 23 single chromatid chromosomes.

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

Spermatogenesis
• Primordial germ cell:- migrate from wall of yolk sac to the
gonads at 4th wks development
• Begins :- 13-16 yrs - old age
• Spermatogonia (type A & B)transferred to spermatozoa
• Spermatogonia -mitotic division -primary spermatocytes
• primary spermatocytes (largest germ cell)-meiosis I - two
secondary spermatocytes
• secondary spermatocytes-meiosis II -four haploid
spermatids
• Spermatids -spermiogenesis -mature sperm

 Condensation of nucleus
 Shading of cytoplasm/unneccessary materials will be
discarded
 Acrosome formation
 Formation of neck and tail
 Many genes &molecular factors are implicated in the
Process of spermatogenesis.
Spermiogenesis:-

1 Axonemal structure, first flagellar
primordium
2 Golgi complex
3 Acrosomal vesicle
4 Pair of centrioles (distal and proximal)
5 Mitochondrion
6 Nucleus
7 Flagellar primordium
8 Microtubules
9 Sperm cells tail
10 Acrosomal cap

The entire spermatogenesis takes about 60-64 days
Regulation of spermatogenesis is by LH & FSH.

• Mature sperms
 Free-swimming, actively motile cells
 consists of a head, neck and a tail
 The head of the sperm forms most of the bulk of the
sperm
and contains the haploid nucleus which is covered by th
Acrosome(saccular organelle ).
• Acrosome contain several enzymes that facilitate penetration
of the zona pellucida and corona radiata of the follicular
cellsduring fertilization
 The tail of the sperm consists :
middle piece, principal and end
piece
 The middle piece contains
mitochondria

Oogenesis
• Oogonia transform to mature oocyte.
• It begins in utero (3rd month) completed with
sexual maturity.
Prenatal maturation of oocyte
Oogonia -mitotic division -primary oocyte
primary oocyte surrounded by follicular epithelia i.e.
primordial follicle
During puberty ,As primary oocyte enlarge follicular
epithelial cell become cuboidal then columnar
forming primary follicle

primary oocyte begin the first meiotic division but
completion of prophase arrest until puberty
OMI (oocyte maturation inhibitor) keep meiotic division of
oocyte arrested- secreted by follicular cells
primary oocyte surrounded by glycoprotein material called
zona pellucida

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

Comparison of male and female gametes
Parameters Oocyte Spermatozoon
Size Massive(0.1mm) Tiny cell(H=5um by 3um, T=50um)
Motility Immotile Actively motile
Cytoplasm Abundant Sparse
Sex
chromosome
One kind, 23 X Two kind, 23X, 23Y
(primary sex
determining)
Miscellaneous
/parts
Surrounded by zona Has head, neck & tail
pellucida & corona radiata

THE BEGINNING OF HUMAN DEVELOPMENT
Gametogenesis
 Conversion of PGCs into Male and Female Gametes.
spermatogenesis and oogenesis
The sequence of gametogenesis is the same, but the timing
of events during meiosis differs in the two sexes.
Involve mitosis , meiosis and cytodifferentiation.
prepares these sex cells for fertilization.

Transportation of gametes
Sperm & oocyte meet in the ampulla
-Oocyte :- is
-by sweeping action of fimbriae
fluid current of cilia in the fimbriae
peristalsis movement of wall of oviduct
-

Sperm transport takes 5 minutes to 7days.
 From seminiferous tubule sperms move passively to
epidydimis, encapacitation (cover of glycoprotein ) will
occur.
 peristaltic movement of vas deferens and fluid from
accessory glands moves it to urethra.
Fructose & Vesiculase enzyme by seminal vesicle

CONDITIONING OF THE SPERMS
The sperms in the female genital tract,
before fertilization undergo
1. Capacitation
2. Acrosome reaction
Capacitation:-
 glycoprotein coat and seminal proteins are removed from
surface of the sperm's acrosome.
 Occur only in the uterus & uterine tubes.
It takes about 7 hours.
 Capacitated sperms show no morphological
change, but more active

Normally=100million sperms per ml of semen
Sperms account for less than 10% of the semen
 Fertile =Sperm motility>50% &Count>20 million/ml of semen.

Acrosome reaction
 occurs during passage of sperm through corona
radiata.
 Outer membrane of the acrosome fuses with overlying cell
membrane of sperm head.
 fused membranes then rupture, producing multiple
perforations
 Hyaluronidase: needed to assist in penetration of the
corona radiata barrier;
 Trypsin-like substances: needed for the digestion of
the zona pellucida;
Acrosin,esterase ,proacrosin,collaginase,aryl sulfatase
& neuraminidase and tubal mucosal enzymes: also needed to
help the sperm cross the zona pellucida and corona radiata

Fertilization :usually occurs in 12 hrs after ovulation.
Complex sequence of events
Begins with contact between a sperm and a
secondary oocyte
Ends with the intermingling of the maternal and
paternal chromosomes and form a Zygote.

Zona reaction/cortical rxn
Prevent polyspermy
 Fusion of plasma membranes
of secondary oocyte and sperm
 head & tail of the sperm
enter the cytoplasm of the
oocyte
Completion of 2nd meiotic
division
Formation of female& male pronucleus.
Fusion of pronuclei to form
Zygote
 chromosomes in the
zygote become arranged on a
cleavage spindle

Importance of Fertilization
1. Restoration of the diploid number of chromosomes
2. Determination of the sex of the new individual
3. Completion of second meiotic division
4. Initiation of cleavage
5. Species variation
6. Perpetuation of species

Cleavage and Blastocyst formation
zygote start to divide.
 begins approximately 30 hours after fertilization
 Rapid increase in the number of blastomeres
Usually in the uterine tube , zygote still in zona pellucida
 day 2-3,12 to 32 blastomeres form morula .

- Tightly align themselves against each other to form a
compact ball of cells - compaction.
-While morula moves to uterus ,a Cavity will form inside
(nourishes the zygote)= the conceptus is called blastocyst
(5th day)
- Inner cells of the morula constitute the Inner cell mass, and
surrounding cells flatten and form the epithelial wall of the
blastocyst, compose the Outer cell mass.
-Blastocyst will differentiate into
embryoblast(inner cell mass) :embryo proper
trophoblast (Outer cell mass): nutrition

 Early pregnancy factor, an immunosuppressant protein,
secreted by the cells that form trophoblast and appears in
the maternal serum within 24 to 48 hours after
fertilization.
 pregnancy test during the first 10 days of development.
 Shedding of the zona pellucida - blastocyst to attaches to
the endometrium = day 6
While floating in the uterus, it derives nourishment from
secretions of the uterine glands.

Second Week of development
Formation of the Bilaminar Embryonic Disc:
 Implantation of the blastocyst is = 6 to 10 days
 Embryoblast produce a bilaminar embryonic disc
(epiblast and hypoblast)
Trophoblast differentiate into
–cytotrophoblast
_syncytiotrophoblast

Trophoblast cytotrophoblast
syncytiotrophoblast
Embryoblast
epiblast hypoblast

Blastocyst
Embryoblast Trophoblast
- Inner cell mass - outer cell mass
- Give embryo proper - give part of placenta
- Project to blastocyst cavity - form wall of blastocyst
hypoblast epiblast syncytiotrophoblast
o
cytotrophoblast
Small high
cuboidal columnar
cells cells
Adjacent Adjacent
to (floor) to the
blastocyst amniotic
cavity cavity
outer
multinucleated
No distinct
boundary
Invasive ,
digestive &
Ingestive
 HCG
Inner
mononucleated
Mitotically
active
Migratory cells

small cavity
appears within
the epiblast =
amniotic cavity

Day 9 &10
Exocoelomic membrane together with the hypoblast, lines
the primary umbilical vesicle or primitive yolk sac.
Lacunae appear in the syncytiotrophoblast = primordial uteroplacental
circulation
lacunae communicate with endometrial capillaries

Day 11 & 12
Cells from the vesicle endoderm form extraembryonic
mesoderm
extraembryonic coelom or chorionic cavity form in extraembryonic
mesoderm
extraembryonic somatic mesoderm
extraembryonic splanchic mesoderm
Lacunar network
Uterine wall defect
completely heal

Extraembryonic structures
-umbilical vesicle (yolk sac)
-Amniotic cavity,amnion
-connecting stalk, and chorionic sac

Day 13
secondary umbilical vesicle
cytotrophoblastic cellular projections form primary chorionic
villi
extraembryonic coelom is now called the chorionic cavity
extraembryonic mesoderm lining the inside of the
the cytotrophoblast known as chorionic plate
• Connecting stalk future umbilical cord ,connect extraembryonic
mesoderm to the chorionic cavity

Day 14
Prechordal plate
develops as a localized thickening of the hypoblast
future site of the mouth
an important organizer of the head region.

Third Week of Development
• Is the period of formation of germ layers and early
tissue and organ differentiation
• Characterized by
• Appearance of primitive streak
• Development of notochord
• Differentiation of three germ layers

GASTRULATION
• A process by which 3 germ layers are formed
• Axial orientation are established
• Beginning of morphogenesis
• Extensive cell shape changes, rearrangement, movement,
and changes in adhesive properties facilitate gastrulation
• Begins with formation of the primitive streak on the
surface of the epiblast

PRIMITIVE STREAK
Thickened linear band in the median plane of the dorsal
aspect of the embryonic disc (15- to 16-day)
 The cephalic end of the streak, the primitive node
surround the primitive pit, a continuous narrow groove forms
in the primitive streak , primitive groove
 Cells of the epiblast migrate toward the primitive streak
detach from the epiblast and slip beneath it

• After cell invagination,
- Some displace the hypoblast, creating the
embryonic endoderm
- Others come to lie between the epiblast and
newly created endoderm to form mesoderm
- Cells remaining in the epiblast then form
ectoderm

In summary ,cells of
epiblast through the process
of gastrulation ,give rise to all
three germ layers
 The primitive streak
normally degenerate
and disappears by
the end of 4th week.
If persist
Sacrococcygeal
teratoma

Notochordal process and notochord
Mesodermal cells migrate cranially from the primitive node
and pit, forming a median cellular cord is called the
notochordal process
This process acquires a lumen, the notochordal canal
The prechordal plate is the primordium of the
oropharyngeal membrane, future site of the oral cavity.

Cells with mesodermal fates migrate cranially on each side
of the notochordal process and meet cranial to the
prechordal plate to form cardiogenic mesoderm in the
cardiogenic area
Caudal to the primitive streak is cloacal membrane, the
future site of the anus

NOTOCHORD
• Rodlike cellular structure formed from notochordal
precursor cells when induced by primitive streak
• Extends from the oropharyngeal membrane to the
primitive node
• Degenerates as the bodies of the vertebrae form, but small
portions of it persist as the nucleus pulposus of each
intervertebral disc

FUNCTION
- Define primordial axis of the embryo and gives its rigidity
- Serve as the base for the development of axial skeleton
- Indicates the future site of vertebral bodies
- Primary inductor of neural plate

The Allantois
Small outpouching from the caudal wall of the umbilical
vesicle to connecting stalk ,day 16
Function:-
Reptiles, mammals and birds
- Reservoir for excretion products of the renal system
- Respiratory function
In humans
Blood formation occurs in its wall during the 3rd - 5th weeks.
Its blood vessel become the umbilical arteries and vein
proximal part persist- urachus or median umbilical
ligament in adults

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

By the end of the 3rd week, the neural folds fuse
and convert the neural plate into a neural tube, the
primordium of the CNS
As the neural folds meet,
Neural tube separates from the surface ectoderm
Neural crest cells changes from epithelial to
mesenchymal and migrate
,

Neural crest cells give rise to sensory ganglia of the
spinal and cranial nerves, ganglia of the autonomic
nervous system, Schwann cells, cells of the adrenal
medulla
Neural crest cells form a flattened irregular mass,
the neural crest
Surface ectoderm differentiates into the epidermis

DEVELOPMENT OF SOMITES
Toward the end of the 3rd week, the paraxial mesoderm
differentiates into paired cuboidal bodies, The somites
Located on each side of the developing neural tube
Form in a craniocaudal sequence
The first pair of somites appears at the end of the 3rd week
38 pairs at (days 20 to 30), 42 to 44 pairs at the end of the
5th week
Used for determining an embryo's age

Development of the intraembryonic coelom
• Intraembryonic coelom divides the lateral mesoderm into
• Somatic or parietal layer_ embryonic body wall
• Splachnic/ visceral layer _ embryonic gut
• Intraembryonic coelom give rise to Pericardial, Pleural and
Peritoneal cavities = 2nd month

Early development of the cardiovascular system
At the end of the 2nd week there is urgent need for
blood vessels to bring blood to the embryo from the
maternal circulation
During the third week, a primordial uteroplacental
circulation develops

Blood vessel formation
Begins in the extraembryonic mesoderm of the umbilical
vesicle, connecting stalk, and chorion
Embryonic b/v formation involves two processes
Vasculogenesis :- the formation of new vascular
channels by assembly of individual cell precursors,
angioblasts
Angiogenesis :- the formation of new vessels by
budding and branching from preexisting vessels

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

Primordial CVS
• Heart and blood vessels arise from mesenchymal cells.
• Paired longitudinal endothelial lined channels endocardial
heart tubes- develop in the cardiogenic area and fuse to form
primordial heart tube
• Tubular heart join with blood vessels in the embryo,
connecting stalk, chorion, and yolk sac to form primordial CVS
.
• 21st day/22nd blood circulation begin and
heart begin to beat
• CVS is the 1st organ system to reach its functional
state

DEVELOPMENT OF CHORIONIC VILLI
• Primary chorionic villi _column of cells -end 2nd week
• Secondary chorionic villi_ early 3rd week
- branched and contain core mesenchymal tissue
Tertiary chorionic vill
- Mesenchymal cell differentiate in to blood vessels
- - Blood vessels are visible
•
- Connected to vessels in the connecting stalk &
to embryonic heart
• Stem cells/ anchoring villi attach to endometrium
• Terminal villi side branches of stem villi
- main exchange of material between mother and
developing embryo.

Fourth to Eighth Weeks:- Period of organogenesis
• Major event
• Development of main organ systems from the three
germ layer but not fully functional except for the
cardiovascular system
• Folding of the embryo and has a distinctly human
appearance
• Risk period to develop congenital anomalies if
exposed to teratogens
2

• How these development occur?
• Growth - cell division and elaboration of cell products
• Morphogenesis: dev’t of shape, size or other features of
body part
• Differentiation: maturation of physiological processes

Folding of the embryo
• Trilaminar embryonic disc - cylindrical embryo
• Results from rapid growth of the embryo
• Occurs in median and horizontal planes
• Effect of craniocaudal folding/median plane
• Before the folding, the structure seen in the midline from the
cranial to caudal side are
• The septum transversum, the developing
Pericardial cavity and heart, the prochordal plate,
the neural plate, the primitive streak and the
cloacal membrane.
3

• After folding, the relative positions of these structures changes
to:
• the developing pericardial cavity lie on the ventral
side of the embryo, ventral to the gut
• the heart now lies in the roof of the pericardial
cavity
• The pericardial coelom lies ventral to the heart and
cranial to the septum transversum which now lies caudalto the
heart, later develop in to central tendon of the diaphragm.

Dorsal view of embryo at 21 days Sagittal section of cranial part of the
embryo at the plane shown in

..After folding͙
- prechordal plate now forms the buccopharyngeal which
closes foregut cranially and when this membrane breaks down,
the foregut communicates with the exterior.
- The developing forebrain grows cranially beyond the
oropharyngeal membrane ,
- Cranial part of the neural tube Forms primordium of the brain
- and distal part of the neural tube-the primordium of the
spinal cord.
- The primitive streak gradually disappears.
- The distal end of the hindgut is closed by cloacal membrane,
at first, this is directed caudally, but later it comes to face
ventrally
5

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

• Paraxial Mesoderm
 Give rise to somites
 end of the fifth week, 42 to 44 pairs are present
• 4 occipital, 8 cervical, 12 thoracic, 5 lumbar,
5 sacral, and 8 to 10 coccygeal pairs
• 1st occipital & last 5-7 coccygeal somites disappear, while
the remaining somites form the axial skeleton
» The number of somites helps to estimate age of
the embryo
15

» Each somite forms its own
• Sclerotome - the cartilage and bone component
• Myotome- providing segmental muscle component
• Dermatome - the segmental skin component
• Each myotome and dermatome also has its own Segmental
nerve component

• Lateral plate mesoderm
 parietal will form serous membranes, peritoneal,
pleural, and pericardial cavities and secrete serous fluid
 visceral layer will form a thin serous membrane around each organ
21-day embryo Section at the end of the 4th week 18

Ectoderm
- Surface ectoderm- epidermis, hair, nail, glands of
the skin, adenohypophysis, enamel, inner ear, lens
of the eye, epithelium of the oral and nasal cavities
and the anus
- Neuroectoderm
• Neural tube- brain, spinal cord, retina, muscles of
the iris, neurohypophysis
• Neural crest- sensory and autonomic ganglia,
adrenal medulla, peripheral glial cells and
pigment cells
• Mesectoderm :- mesenchyme of the head, skull
bones, and meninges, muscles of the head,
dentine and cement
19

Main events in specific weeks
Fourth Week
The neural tube is formed opposite the somites and widely
open at the rostral and caudal neuropores
By 24 days, the first two pharyngeal arches (mandibular
and hyoid) are visible
The heart produces a large ventral prominence and pumps
blood.
By 26 days 3 pairs of pharyngeal arches are visible and the
rostal neuropore closed
21

....events of 4th week
The forebrain produces a prominent elevation of the head
Upper limb buds form by day 26 or 27 on the ventrolateral
body walls
The otic pits and lens placodes appear
End of the fourth week- 4th pair of pharyngeal arches and
the lower limb buds and caudal eminence form
23

Week 5
• Bones appear during week 5 as mesenchymal
condensations in the limb buds
• Upper limbs show regional differentiation with developing
hand plates
• Mesonephric ridges indicate the site of the mesonephric
kidneys
• Rapid development of the brain and facial prominences
25

Sixth Week
• Embryo show reflex response to touch
• The upper limbs begin to show regional differentiation(elbows,
handplates and digital rays develop)
• The clavicle develops by intramembranous ossification and
later develops articular cartilages
• Embryos in the sixth week show spontaneous movements, such
as twitching of the trunk and limbs
27

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

Week 7
• Loose mesenchyme between the digital rays break down
and notches appear between the digital rays in the hand
plates.
• Digital rays form in the foot plate
• Ossification of the bones of the upper limbs has begun
48 days
9

Eighth Week
• Digits of hand separates
• Scalp vascular plexus
• Ossification in the bones of lower limb
• Evidence of caudal eminence disappear
• Sex differences exist
• Embryo has distinct human characteristics
• Notches are clearly visible b/n digital rays of the feet
approximately 56 days
0

• Methods of embryo age estimation
• The day of onset of the LNMP
• The estimated time of fertilization
• Ultrasound measurements of the chorionic sac and embryos
• Examination of external characteristics of the embryo
• Methods of measurements
• Greater length (GL)- when straight
• Sitting height or crown-rump length (CRL)
• Standing height or crown- heel length (CHL)
31

Carnegie stages
• The embryo can be classified according to age, size or
morphologic characteristics. The correlation b/n these three
criteria will allow identifying embryonic Carnegie stages
• First week ,day 1, 0.1-0.15mm, stage 1, fertilization
• Day 1. stage 2,first cleavage
• Day 4,stage 3, blastocyst free in the uterine tube
• Day 5-6, stage 4, blastocyst hatches & begins implantation
• Week 2
• Day 7-12, 0.1-0.2mm, stage 5, blastocyst fully implanted
• Day 13, 0.2mm, stage 6, primary stem villi form, primitive streak
• Week 3
• Day 15-16, 0.4mm, stage 7, gastrulation, notochord process
• Day 17-18, 1-1.5mm, stage 8, neural plate &neural groove
• Day 20-21, 1.5-2.5mm, 1-3 somites, stage 9,head fold, neuromeres,
neural fold, heart beat & pump blood
32

• Week 4
• Day 22-23, 2-3.5mm, 4-12 somites, stage 10,neural
tube, pairs of pharyngeal arches, embryo curve
• Day 24-25, 2.5-4.5mm,13-20 somites, stage 11, head &
tail folding, rostral neuropore closed otic placodes, otic
vesicles
• Day 26-27, 3-5mm,21-29 somites, stage 12, UL buds,
caudal neuropore closed third pair pharyngeal arches
• Day 28-30,4-6mm, 30-35 somites, stage 13,c-
shaped,four pair of pharyngeal arch, lower limb buds
• Week 5
• Day 31-32, 5-7mm, 36-44 somites, stage 14,uper limb buds paddle
shaped, otic cups, lens pits
• Day33-36, 7-9mm, stage 15,hand plate, digital rays, cervical sinus
33

• Week 6
• Day 37-40,stage 16 8-11mm, stage 16, foot plate, pigment in
retina, auricular hillocks
• Day 41-43, 11-14mm, stage 17, digital rays clear in hand plate,
trunk beginning to straighten, outline future auricle of external ear
• Week 7
• Day 44-46, 13-17mm,stage 18, digital rays clear in foot plate,
elbow region visible, eyelids forming, notches b/n digital rays in
the hand plate, nipple visible
• Day 47-48, 16-18mm, stage19, limb extend ventrally, midget
herniation, trunk elongating
• Week 8
• Day 49-51,18-22mm, stage 20, UL longer & bent at elbow, finger
distinct, notches b/n digital rays in foot, scalp vascular plexus
• Day52-53, 22-24mm,stage 21, hands & feet approach, fingers are
free, toes distinct
34

• Day 54-55, 23-28mm, stage 22, toes free& longer,
eyelids and auricles of external ear more developed.
• Day 56, 27-31mm, stage 23, head more rounded,
external genitalia but sexless, caudal eminence
disapear.
35

FETAL PERIOD
9th wk - birth.
Characteristics:-
» Differentiation of Tissues,& Organ systems
» Rapid growth of the body»
Relative slow down in growth of head
36

FETAL PERIOD
9 week fetus
9 - 12 weeks
Head= ½ CHL
Face - broad, eyes widely
separated & move to
ventral side, but eyelids
closed ,
 ears lie at the side
of the head.
At 9th weeks liver -
erythropoiesis.

9 - 12 week cont… 12 week fetus
By 11th wk intestinal coils
returned to the abdomen
By the end of 12th wk
upper limb reach final
relative length
Primary ossification
center- in skull and
long bones
erythropoiesis is by
spleen
External genitalia
distinguished by
ultrasound
Urine formation begins
between the 9th and
12th weeks

13-16 weeks
14th wk coordinated limb
movement - not felt
by the mother
Active ossification of fetal
skeleton is - visible bone by
ultrasound
At 14th wk slow eye
movement occur
By 16th wks Ovaries contain
primordial ovarian follicles
that includes oogonia
By 12-14 wks sex of external
genitalia are recognized
13th wk

17 - 20 weeks
Growth slow down
Quickening
Vernix caseosa: dead epidermal
cells and a fatty substance, prevent
skin from abrasions, chapping, and
hardening
Eye brows & head hairs visible
at 20 wks
Body covered by lanugo
Brown fat formed- produce
heat
By 18 wks - uterus is formed
- canalization of the vagina
By 20 wks testes&ovaries begun to descend
40

21- 25 week
Substantial weight gain
Skin wrinked
At 21wks rapid eye mov’t begin
By 24 wks - type II alveolar cell produce surfactant
Finger nail present
Survive if born prematurely if given intensive care
25-week-old
41

26- 29 weeks
At 26 wks eye lids open, lanugos & head hair well
developed.
Toe nail become visible
The quantity of white fat increased.
Spleen has been site of erythropoiesis
By 28 wks erythropoiesis - bone marrow
The lungs and pulmonary vasculature have developed
sufficiently
Central nervous system has matured
42

30- 34 weeks
By 30 wks eye pupillary reflex can be elicited
By the end of this period skin is pink & smooth
Quantity of white fat = 8% of body wt
Fetuses 32 wks & older usually survive if born prematurely
43

35 - 38 weeks
Fetuses at 35 weeks have a firm grasp
Male fetus longer and heavier than Females
The thorax (chest) is prominent
Breasts often protrude slightly in both sexes
In full term male the testis is usually in -scrotum
At birth -weight 3000-3,400gm, CRL- 36cm & CHL -50cm
44

Estimation of fetal age
1st trimester
- Crown rump length
2nd & 3rd trimesters
-Biparietal diameter
-Head circumference
-Abdominal circumference
-Femoral length
-Foot length
46

Expected date of delivery
• The EDD of fetus is 266 days or 38 weeks after fertilization,
i.e, 280 days or 40 weeks after LNMP.
Count back 3 months from the first day of the LNMP and
add a year and 7 days(LNMP-3months+ year + 7 days)
Ultrasound examinations
47

The Placenta and Fetal Membranes
Separate the fetus from the endometrium
Area of exchange b/n the mother and fetus
Are programmed to develop and aged faster than
the fetal body
The fetal membrane includes
Chorion
Amnion
Umbilical vesicle
Allantois
49

Chorion
• Formed by extraembryonic somatic mesoderm and
cytotrophoblast and syncytiotrophoblast cells
• Has two parts
• smooth chorion:- chorion laeve
» Found in abembryonic pole
» Villi degenerate, by compression of decidua
capsularis and reducing the blood supply
• Villous chorion, chorion frondosum (bushy chorion
» branched profusely, and enlarged villi
» Located at embryonic pole
» Form fetal portion of the placenta
50

THE PLACENTA
• Fetomaternal organ that is primary site of nutrient and ga
exchange between the mother and fetus.
• Has two components
- A fetal part that develops from Villous chorion
- A maternal part that is derived from decidua basalis
• The Decidua
• Refers to the gravid endometrium
• The functional layer of the endometrium, which is
shed during parturition
• Show decidual reaction (endometrial cellular and
vascular change as a result of pregnancy)
• Decidual cells contain glycogen and
lipid
that are nutritive for the embryo and prevent
uncontrolled invasion by the syncytiotrophoblas
55

THE PLACENTA
• The Decidua
• The three parts
• The decidua basalis -
• deep to the conceptus
• Forms the maternal part of the
placenta
• The decidua capsularis
• superficial part of the
decidua
overlying the conceptus
• With growth of the chorionic
vesicle,
this layer becomes stretched and
degenerates
• The decidua parietalis
• Is all the remaining parts of the
decidua
57

Structure of the Placenta
The fetal part of the placenta (villous chorion) has 2 type
of villi
Stem villi- anchor the decidua
basalis
Freely branching villi- project into the
intervillous space for
exchange
• The maternal part of the placenta is formed by the
decidua basalis
- villi invade the decidua basalis and form
placental septa that project toward the chorionic plate- The
placental septa divide the placenta
into irregular convex areas-cotyledon
- By the end of the 4th month, the decidua basalis is
almost entirely replaced by the cotyledons 59

͙
• The fetal border of the placenta is covered by amniotic
membrane with umbilical cord attached to it
• The maternal border is roughed by cotyledons and covered
by cytotrophoblastic shell
• Full-term Placenta
Is discoid
-a diameter of 15 to 25 cm,
-3 cm thick, and
-weighs about 500 to 600 g
At birth, it is torn from the uterine wall and, 30 minutes
after the baby, is expelled
•
60

A full-term placenta.
A. Fetal side B. Maternal side
61

The Placental Membrane
• The maternal and fetal bloods do not mix
with each other
• They are separated by a membrane, made up
- The endothelium of fetal blood vessels, and
its basement membrane
- Surrounding mesoderm ( CT)
- Cytotrophoblast, and its basement
membrane
- Syncytiotrophoblast
• After the 20th week, the cytotrophoblast disappear.
Most drugs and other substances in the maternal plasma
pass through the placental membrane 62

The Placental Membrane
• All interchanges takes place through this
membrane and its total surface area varies from
4-14 m2
• Absorptive area is greatly increased by the
presence of numerous micro villi on the surface
syncytiotrophoblast
• Transport of molecules can be by
• Simple diffusion- O2 & CO2
• Facilitated diffusion- glucose
• Active transport- many ions
• Pinocytosis- maternal antibodies
63

Placental Circulation
• begin as early as the 9th day of pregnancy
• Maternal blood in the intervillous spaces is constantly in
circulation
• Blood enters intervillous spaces is through 80 to 100 spiral
endometrial arteries
• The intervillous space of the mature placenta contains ~150
mL of blood w/c is replenished 3 or 4x per minute
64

• Poorly oxygenated blood leaves the fetus through the
umbilical arteries to the placenta.
• The umbilical veins carries oxygen-rich blood to the fetus

Function Of The Placenta
• Exchange of Nutrients and Electrolytes
• such as amino acids, free fatty acids, carbohydrates,
and vitamins b/n fetal and maternal blood
• Exchange of Gases:- such as oxygen, carbon dioxide, and carbon monoxide
• Transmission of Maternal Antibodies -immunoglobulin G (IgG)
• Synthesis of several hormones-
» Progesterone-essential for maintenance of pregnancy
after the 4th month
» Estrogens-promote uterine growth and development
of mammary gland
» HCG-used as a test to detect pregnancy in its early
stage, maintains the corpus luteum, preventing the onset of
menstrual periods
» Somatomammotropin-has anti-insulin effect on the mother leading to
increase plasma level of glucose and amino acid in the maternal circulation
» Melanin spreading factors- cause discoloration of
areola 67

Abnormalities of the Placenta
• Its abnormalities could be regarding to different factors,
these are:
• Abnormal shape
• Placenta bilobata: consists of two equal lobes
connected by placental tissue
• Placenta bipartita: consists of two equal
parts connected by membrane
• Placenta Succenturiata: consists of a large lobe and
a smaller one connected together by membrane
• Abnormal position: placenta previa- internal os of the uterus.
• Abnormal adhesion:
- Placenta accreta- the chorionic villi penetrates deeply in to
the uterine wall to reach the myometrium
- Placenta percreta -reaches the peritoneal coat 69

:
• Abnormality in diameter
• Abnormality in weight
• Placental lesions:
• Placental infarct
• Placental tumor
• Abnormal umbilical cord attachment
• marginal(battledore Placenta)
71

Umbilical Cord
• Arise from primitive umbilical ring, at the 5th
week the ring contain
• connecting stalk, containing the
allantois and the umbilical vessels
• yolk stalk (vitelline duct) accompanied
by the vitelline vessels
• Attachment to the placenta usually near the
center of the fetal surface.
• Umbilical vessels (two arteries and one vein)
surrounded by the jelly of Wharton
• 1-2cm in diameter and 30-90cm in
length
72

The Umbilical Vesicle (Yolk Sac)
• Is the secondary yolk sac developed by shrinking of
primary yolk sac.
• Importance of yolk sack
• transfer of nutrients during
the 2nd -3rd
• Blood development from 3rd week
– 6th week
• the endoderm of the umbilical vesicle is
incorporated into the embryo as the primordial
gut
• PGCs appear its wall in 2-3rdwk

• Fate of yolk sac
• By 6th wk yolk stalk get detached from midgut
loop
• By 9th wk the yolk sac shrink
• By 20 wk usually not visible
• 2-4% of adults, the proximal intra-
abdominal part may persists as an ileal
diverticulum (Meckel diverticulum)

Amniotic Fluid
It is a clear pale, slightly alkaline fluid that fill
amniotic cavity.
• its amount reaches 800 to 1000 ml at 37 weeks
• It is composition of water (98-99%), carbohydrates,
proteins,lipids, hormones, minerals and desquamated
epithelial cells, meconium and urine.
• is swallowed by the fetus and absorbed by the
fetal respiratory and digestive tracts
• Origin:-- Fetal- active secretion from amniotic
epithelium
• transudation from the fetal circulation
• fetal urine
- Maternal- transudation from the
maternal circulation,decidua perietalis
78

Amniotic Fluid
• function:
Protects the fetus against injury
A medium for free fetal movement
Maintains the fetal temperature
Source of nutrition
Medium for fetal excretion
The forebag of water helps the dilatation of cervix
during labour
Antiseptic for birth canal
Assists in maintaining homeostasis of fluid & electrolytes
Permits symmetric external growth of the fetus
• Polyhydramnios:- excess of amniotic fluid (1500-
2000ml)
• Oligohydramnios - decreased amount (less than 400 ml)

PARTURITION
• Is the process during which the fetus, placenta, and fetal
membranes are expelled from the mother's reproductive
tract by Labor
• The factors that trigger labor are hormones like oxytocin,
Estrogens and prostaglandins
• Labor is a continuous process
- Dilation:-
• progressive dilation of the cervix and ends
when the cervix is completely dilated
81

͙
- Expulsion
• Delivery of the baby
- The placental stage
• Expulsion of the placenta and
membranes.
- Recovery stage
• Myometrial contraction - spiral aa
constrict
82

MULTIPLE PREGNANCIES
• Is pregnancy carrying more than one fetus.
- Dizygotic Twins
-Result from two oocytes ,fertilized by different
spermatozoa from same father or different father
(superfecundation)
)
- have no more resemblance than any other
brothers or sisters
-zygotes implant individually in the uterus, and
usually each develops its own placenta, amnion
, and chorionic sac
• When the twins are implanted more closer the two
placentas and chorionic sacs fuse together
86

MULTIPLE PREGNANCIES
• Monozygotic (Identical) twins
• Develops from a single fertilized ovum
• They result from splitting of the zygote at various
stages of development
• Two-cell stage separation
• The blastocysts implant
separately, and each embryo has its own placenta
and chorionic sac and amniotic cavity
• resembles dizygotic twins
• Splitting early blastocyst stage
• most common
• The two embryos have a common placenta and a common
chorionic cavity, but separate amniotic cavities
87

• Separation at the bilaminar germ disc stage
• common placenta , a common
chorionic & amniotic sac
• Division at later developmental stage
• Incomplete division of the axial area and resultin
Conjoined twins
• One of the Conjoined twins may be very small
(parasitic twin) and the other may be fully
developed
88

OTHER TYPES OF MULTIPLE
PREGNANCIES͙
• Triplets may be derived from
• 1 zygote split and be
identical
• 2 zygotes , identical twins & a
singleton
• 3 zygotes and be of the same
sex or of different sexes
 quadruplets, quintuplets, sextuples
͙
91

Teratology
• is the branch of science that studies the causes,
mechanisms, and patterns of abnormal
development.
• A fundamental concept in teratology is that
certain stages of embryonic development are
more vulnerable to disruption than others.

TERATOLOGY
• Congenital anatomic anomalies or birth
defects or congenital malformations are
developmental disorders present at birth.
• Includes Structural, functional, metabolic,
behavioral, or hereditary.
• leading cause of infant mortality .

• Until the 1940s, it was generally believed that
human embryos were protected from
environmental agents such as drugs and
viruses by their extraembryonic/fetal
membranes (amnion and chorion) and their
mothers' abdominal and uterine walls

• In 1941, the first well-documented cases were
reported that an environmental agent (rubella
virus) could produce severe anatomic
anomalies, such as cataracts, cardiac defects,
and deafness if the rubella infection was
present during the critical period of
development of the eyes, heart, and ears.

• Severe limb anomalies and other
developmental disruptions were found in
infants of mothers who had consumed a
sedative called thalidomide during early
pregnancy.

• Factors affecting teratogens to produce birth
defects/principles of teratology
• Genotype of the conceptus &how it interacts
with env’t
• Developmental stage at the time of
exposure-
» The first two wks- teratogens may kill or no effect at
all
» Embryonic period- sensitive period ,result in
birth defect
» Fetal period- cause functional defect
• Dose and duration of exposure to a
teratogens
» The greater the time of exposure to teratogens the
more
severe effect
• Mechanisms of action of a teratogens differs.
• Manifestations are death,malformation,growth
retardation and functional disorders. 97

causes
• The causes of congenital anatomic anomalies or
birth defects are often divided into:
• Genetic factors such as chromosome
abnormalities
• Environmental factors such as drugs and viruses
• multifactorial inheritance (genetic and
environmental factors acting together in a
complex manner

• For 50% to 60% of congenital anomalies, the etiology
is unknown .
• The anomalies may be single or multiple and of major
or minor clinical significance.
• Single minor anomalies are present in approximately
14% of newborns. Anomalies of the external ear, for
example, are of no serious medical significance, but
they indicate the possible presence of associated major
anomalies.
• For example, the presence of a single umbilical artery
alerts the clinician to the possible presence of
cardiovascular and renal anomalies.

• Ninety percent of infants with three or more minor
anomalies also have one or more major defects.
• Of the 3% born with clinically significant congenital
anomalies, 0.7% have multiple major defects.
• Most of these infants die during infancy. Major
developmental defects are much more common in early
embryos (10%-15%); however, most of them abort
spontaneously during the first 6 weeks.
• Chromosome abnormalities are present in 50% to 60%
of spontaneously aborted embryos

ANOMALIES CAUSED BY
GENETIC FACTORS
• Numerically, genetic factors are the most
important causes of congenital anomalies.
• It has been estimated that they cause
approximately one third of all congenital
anatomic anomalies .
• Nearly 85% of all anomalies have no known
causes. Any mechanism as complex as mitosis
or meiosis may occasionally malfunction.
• Chromosomal abnormalities or aberrations are
present in 6% to 7% of zygotes (single-cell
embryos).

• Many of these early abnormal embryos never
undergo normal cleavage and become
blastocysts.
• In vitro studies of cleaving zygotes less than 5
days old have revealed a high incidence of
abnormalities.
• More than 60% of day 2 cleaving zygotes were
found to be abnormal.
• Many defective zygotes, blastocysts, and 3-
week embryos abort spontaneously, and the
overall frequency of chromosome
abnormalities in these embryos is at least 50%

• Two kinds of change occur in chromosome
complements: numerical and structural.
• The changes may affect the sex chromosomes
and/or the autosomes-chromosomes other than
sex chromosomes.
• In some instances, both kinds of chromosome are
affected.
• Persons with chromosome abnormalities usually
have characteristic phenotypes (morphologic
characteristics), such as the physical
characteristics of infants with Down syndrome .

• They often look more like other persons with the same
chromosome abnormality than their own siblings
(brothers or sisters).
• This characteristic appearance results from genetic
imbalance.
• Genetic factors initiate anomalies by biochemical or
other means at the subcellular, cellular, or tissue level.
• The abnormal mechanisms initiated by the genetic
factors may be identical or similar to the causal
mechanisms initiated by a teratogen, for example, a
drug

Numerical Chromosomal
Abnormalities
• In the United States, approximately one in 120
live-born infants has a chromosomal abnormality.
• Numerical aberrations of chromosomes usually
result from nondisjunction, an error in cell
division in which there is failure of a
chromosomal pair or two chromatids of a
chromosome to disjoin during mitosis or meiosis.
• As a result, the chromosomal pair or chromatids
pass to one daughter cell and the other daughter
cell receives neither .

• Nondisjunction may occur during maternal or
paternal gametogenesis .
• The chromosomes in somatic cells are
normally paired; they are called homologous
chromosomes (homologs).
• Normal human females have 22 pairs of
autosomes plus two X chromosomes, whereas
normal males have 22 pairs of autosomes plus
one X chromosome and one Y chromosome

• A congenital anatomic anomaly or birth defect
is a structural abnormality of any type; however,
not all variations of development are anomalies.
• Anatomic variations are common, for example,
bones vary among themselves, not only in their
basic shape but in lesser details of surface
structure.
• There are four clinically significant types of
congenital anomalies: malformation, disruption,
deformation, and dysplasia

• Malformation: A morphologic defect of an
organ, part of an organ, or larger region of the
body that results from an intrinsically
abnormal developmental process.
• Intrinsic implies that the developmental
potential of the primordium is abnormal from
the beginning, such as a chromosomal
abnormality of a gamete at fertilization.

• Most malformations are considered to be a defect
of a morphogenetic or developmental field that
responds as a coordinated unit to embryonic
interaction and results in complex or multiple
malformations.
• Disruption: A morphologic defect of an organ,
part of an organ, or a larger region of the body
that results from the extrinsic breakdown of, or an
interference with, an originally normal
developmental process.

• Thus, morphologic alterations after exposure
to teratogens-agents such as drugs and
viruses-should be considered as disruptions.
• A disruption cannot be inherited, but inherited
factors can predispose to and influence the
development of a disruption.

• Deformation: An abnormal form, shape, or
position of a part of the body that results
from mechanical forces.
• Intrauterine compression that results from
oligohydramnios-insufficient amount of
amniotic fluid-produces an equinovarus foot
or clubfoot , an example of a deformation
produced by extrinsic forces.

• Some central nervous system defects, such as
meningomyelocele-a severe type of spina
bifida-produce intrinsic functional
disturbances that also cause fetal deformation.
• Dysplasia: An abnormal organization of cells
into tissue(s) and its morphologic result(s).

• Dysplasia is the process and the consequence
of dyshistogenesis (abnormal tissue
formation).
• All abnormalities relating to histogenesis are
therefore classified as dysplasias, e.g.,
congenital ectodermal dysplasia .

• Dysplasia is causally nonspecific and often
affects several organs because of the nature of
the underlying cellular disturbances
• Other descriptive terms are used to describe
infants with multiple anomalies and terms have
evolved to express causation and pathogenesis.

• A polytopic field defect is a pattern of
anomalies derived from the disturbance of a
single developmental field.
• A sequence is a pattern of multiple anomalies
derived from a single known or presumed
structural defect or mechanical factor.

• A syndrome is a pattern of multiple
anomalies thought to be pathogenetically
related and not known to represent a single
sequence or a polytopic field defect.
• An association is a nonrandom occurrence
in two or more individuals of multiple
anomalies not known to be a polytopic field
defect, sequence, or syndrome

• Whereas a sequence is a pathogenetic and not a causal
concept, a syndrome often implies a single cause, such
as trisomy 21 (Down syndrome).
• In both cases, however, the pattern of anomalies is
known or considered to be pathogenetically related.
• In the case of a sequence, the primary initiating factor
and cascade of secondary developmental complications
are known.
• For example, the Potter sequence, attributed to
oligohydramnios, results from either renal agenesis or
leakage of amniotic fluid.

• An association, in contrast, refers to
statistically, not pathogenetically or causally,
related defects. One or more sequences,
syndromes, or field defects may very well
constitute an association.

• Dysmorphology is an area of clinical genetics
that is concerned with the diagnosis and
interpretation of patterns of structural defects.
• Recurrent patterns of birth defects are the
hallmarks of syndrome recognition.
• Identifying these patterns in individuals has
resulted in improved understanding of the
etiology and pathogenesis of these conditions

Aneuploidy and Polyploidy
• Changes in chromosome number represent
either aneuploidy or polyploidy.
• Aneuploidy is any deviation from the human
diploid number of 46 chromosomes.
• An aneuploid is an individual who has a
chromosome number that is not an exact
multiple of the haploid number of 23 (e.g., 45
or 47).

• A polyploid is an individual who has a
chromosome number that is a multiple of the
haploid number of 23 other than the diploid
number (e.g., 69; )
• The principal cause of aneuploidy is
nondisjunction during cell division , resulting
in an unequal distribution of one pair of
homologous chromosomes to the daughter
cells.

• One cell has two chromosomes and the other
has neither chromosome of the pair.
• As a result, the embryo's cells may be
hypodiploid (45, X, as in Turner syndrome )
or hyperdiploid (usually 47, as in trisomy 21
or Down syndrome ).
• Embryos with monosomy-missing a
chromosome-usually die. Approximately
99% of embryos lacking a sex chromosome
(45, X) abort spontaneously

MONOSOMY
Turner Syndrome
• Usually die.
• Approximately 99% of embryos lacking a sex
chromosome (45, X) abort spontaneously
• The phenotype of Turner syndrome is female
• Source is in the paternal gamete (sperm) in
approximately 75% of cases

• Features
– Short stature, short and webbed neck
– Prominent ears
– Redundant skin at the back of neck
– Defective gonadal development
– Lymphydema of the limbs

Turner Syndrome
• Approximately 1% of monosomy X female embryos
survive.
• The incidence of 45, X or Turner syndrome in newborn
females is approximately 1 in 8000 live births.
• Half of the affected individuals have 45, X; the other
half have a variety of abnormalities of a sex
chromosome. The phenotype of Turner syndrome is
female .
• Secondary sexual characteristics do not develop in 90%
of affected girls, and hormone replacement is required.

• Phenotype refers to the morphologic
characteristics of an individual as determined
by the genotype and the environment in which
it is expressed.
• The monosomy X chromosome abnormality is
the most common cytogenetic abnormality
observed in live-born humans and fetuses that
abort spontaneously ; it accounts for
approximately 18% of all abortions caused by
chromosome abnormalities.

• The error in gametogenesis
(nondisjunction) that causes monosomy X
(Turner syndrome), when it can be traced, is
in the paternal gamete (sperm) in
approximately 75% of cases, that is, it is the
paternal X chromosome that is usually
missing.
• The most frequent chromosome constitution
in Turner syndrome is 45, X; however,
nearly 50% of these people have other
karyotype

Trisomy of Autosomes
• The presence of three chromosome copies in a
given chromosome pair is called trisomy.
• Trisomies are the most common abnormalities
of chromosome number.
• The usual cause of this numerical error is
meiotic nondisjunction of chromosomes ,
resulting in a gamete with 24 instead of 23
chromosomes and subsequently in a zygote
with 47 chromosomes.

Trisomy of the autosomes is associated with
three main syndromes :
• Trisomy 21 or Down syndrome
• Trisomy 18 or Edwards syndrome
• Trisomy 13 or Patau syndrome

TRISOMIES:Autosomes
Down syndrome (trisomy 21)
• by an extra copy of chromosome 21.
• 75% will die and get aborted
• The incidence increases with maternal age.
• Features
• Mental deficiency;
• brachycephaly,
• flat nasal bridge;
• upward slant to palpebral fissures;
• protruding tongue;
.
103

• simian crease;
• clinodactyly of fifth digit;
• congenital heart defects;
• gastrointestinal tract abnormalities

TRISOMY 18(Edwards syndrome)
• 85% are lost b/n 10 wks of gestation or if born alive
usually die by age 2 months.
• features:
• mental retardation
• congenital heart defects
• low-set ears, and flexion of fingers and hands
• renal anomalies, syndactyly
• malformations of the skeletal system
105

prominent occiput, cleft lip, low-set ears, and one or more flexed fingers

TRISOMY 13(Patau syndrome)
• Over 90% of the infants die in the first month
• Characteristics
• Mental retardation
• deafness,
• cleft lip and palate,
• eye defects,
• congenital heart defects
107

cleft lip and palate, the sloping forehead and microphthalmia, polydactyl

TRISOMIES of Sex chromosomes
• Trisomy(3) of the sex chromosomes is a
common disorder
• no characteristic physical findings in infants or
children
• chromosome (DNA) analysis today

Klinefelter's syndrome (XXY ):
• small testes,
• hyalinization of seminiferous tubules;
• aspermatogenesis;
• often tall with disproportionately long lower
limbs.
• Intelligence is less than in normal siblings.
• Approximately 40% of these males have
gynecomastia

• Infants with trisomy 13 and trisomy 18 are severely
malformed and mentally retarded and usually die
early in infancy.
• More than half of trisomic embryos spontaneously
abort early.
• Trisomy of the autosomes occurs with increasing
frequency as maternal age increases.

• For example, trisomy 21 occurs once in
approximately 1400 births in mothers ages 20
to 24 years, but once in approximately 25
births in mothers 45 years and older .

Tetrasomy and pentasomy
• of the sex chromosomes also occur.
• Persons with these abnormalities have four or
five sex chromosomes, respectively; the following
chromosome complexes have been reported in
females: 48, XXXX and 49, XXXXX; and males:
48, XXXY, 48, XXYY, 49, XXXYY, and 49,
XXXXY.

• The extra sex chromosomes do not accentuate
sexual characteristics;
• greater the severity of mental retardation and
physical impairment
• Errors in meiosis occur with increasing
maternal age, and the most common
aneuploidy seen in older mothers is trisomy
21.

• Because of the current trend of increasing
maternal age, it has been estimated that by the
end of this decade, children born to women
older than 34 years will account for 39% of
infants with trisomy 21.
• Translocation or mosaicism occurs in
approximately 5% of the affected children.

• Mosaicism, two or more cell types containing
different numbers of chromosomes (normal
and abnormal), leads to a less severe
phenotype and the IQ of the child may be
nearly normal

• Sex chromatin studies were useful in the past
for detecting some types of trisomy of the
sex chromosomes because two masses of sex
chromatin are present in nuclei of XXX
females (trisomy X) and nuclei of XXY
males (Klinefelter syndrome) contain a mass
of sex chromatin .
• Today, diagnosis is best achieved by
chromosome (DNA) analysis

Mosaicism
• A person who has at least two cell lines with two
or more different genotypes (genetic
constitutions) is a mosaic.
• Either the autosomes or sex chromosomes may
be involved.
• Usually the anomalies are less serious than in
persons with monosomy or trisomy, e.g., the
features of Turner syndrome are not as evident in
45, X/46, XX mosaic females as in the usual 45, X
females.

• Mosaicism usually results from nondisjunction
during early cleavage of the zygote .
• Mosaicism resulting from loss of a
chromosome by anaphase lagging also occurs;
the chromosomes separate normally but one
of them is delayed in its migration and is
eventually lost

Triploidy
• The most common type of polyploidy is triploidy
(69 chromosomes).
• Triploid fetuses have severe intrauterine growth
retardation with a disproportionately small trunk
.
• Several other anomalies are common.
• Triploidy could result from the second polar body
failing to separate from the oocyte during the
second meiotic division ; but more likely triploidy
results when an oocyte is fertilized by two sperms
(dispermy) almost simultaneously.

• Triploidy occurs in approximately 2% of
embryos, but most of them abort
spontaneously.
• Triploid fetuses account for approximately
20% of chromosomally abnormal
miscarriages.
• Although triploid fetuses have been born
alive, this is exceptional.
• These infants all died within a few days
because of multiple anomalies and low birth
weight

Tetraploidy
• Doubling the diploid chromosome number to
92 (tetraploidy) probably occurs during the
first cleavage division.
• Division of this abnormal zygote would
subsequently result in an embryo with cells
containing 92 chromosomes

Structural Chromosomal Abnormalities
• Most abnormalities of chromosome structure
result from chromosome breakage followed by
reconstitution in an abnormal combination .
• Chromosome breakage may be induced by
various environmental factors, for example,
radiation, drugs, chemicals, and viruses.

• The resulting type of structural chromosome
abnormality depends on what happens to the
broken pieces.
• The only two aberrations of chromosome
structure that are likely to be transmitted from
parent to child are structural rearrangements,
such as inversion and translocation

Translocation
• This is the transfer of a piece of one chromosome to a
nonhomologous chromosome.
• If two nonhomologous chromosomes exchange pieces,
it is a reciprocal translocation .
• Translocation does not necessarily cause abnormal
development.
• Persons with a translocation between a number 21
chromosome and a number 14 chromosome, for
example , are phenotypically normal.

• Such persons are balanced translocation carriers.
• They have a tendency, independent of age, to
produce germ cells with an abnormal translocation
chromosome.
• Three percent to 4% of persons with Down
syndrome have translocation trisomies, that is, the
extra 21 chromosome is attached to another
chromosome

DELETION
• When a chromosome breaks, part of it may be
lost .
• A partial terminal deletion from the short arm
of chromosome 5 causes the cri du chat
syndrome .
• Affected infants have a weak catlike cry,
microcephaly (abnormally small head), severe
mental deficiency (retardation), and congenital
heart disease.

• A ring chromosome is a type of deletion
chromosome from which both ends have been
lost, and the broken ends have rejoined to form a
ring-shaped chromosome .
• Ring chromosomes are rare but have been found
for all chromosomes.
• These abnormal chromosomes have been
described in persons with Turner syndrome,
trisomy 18, and other structural chromosomal
abnormalities

Duplications
• These abnormalities may be represented as a
duplicated part of a chromosome, within a
chromosome , attached to a chromosome, or as
a separate fragment.
• Duplications are more common than deletions
and are less harmful because there is no loss of
genetic material.
•

• However, there is often a resulting clinical
effect on the phenotype leading to either
mental impairment or birth defects in
individuals with chromosome duplication.
• Duplication may involve part of a gene, a
whole gene, or a series of genes

Inversion
• This is a chromosomal aberration in which a
segment of a chromosome is reversed.
• Paracentric inversion is confined to a single arm
of the chromosome , whereas pericentric
inversion involves both arms and includes the
centromere.
• Carriers of pericentric inversions are at risk of
having offspring with abnormalities because of
unequal crossing over and malsegregation at
meiosis

Isochromosomes
• The abnormality resulting in
isochromosomes occurs when the
centromere divides transversely instead of
longitudinally .
• An isochromosome is a chromosome in
which one arm is missing and the other
duplicated.

• An isochromosome appears to be the most
common structural abnormality of the X
chromosome.
• Persons with this abnormality are often short
in stature and have other stigmata of Turner
syndrome.
• These characteristics are related to the loss of
an arm of an X chromosome

Anomalies Caused by Mutant Genes
• Seven percent to 8% of congenital anomalies
are caused by gene defects .
• A mutation usually involves a loss or change
in the function of a gene and is any
permanent, heritable change in the sequence
of genomic DNA.

• Because a random change is unlikely to lead
to an improvement in development, most
mutations are deleterious and some are lethal
• The mutation rate can be increased by a
number of environmental agents, such as
large doses of radiation.

• Anomalies resulting from gene mutations are
inherited according to mendelian laws;
consequently, predictions can be made about
the probability of their occurrence in the
affected person's children and other relatives.
• An example of a dominantly inherited
congenital anomaly-achondroplasia -results
from a G-to-A transition mutation at
nucleotide 1138 of the cDNA in the fibroblast
growth factor receptor 3 gene on chromosome
4p.

Gene Mutations
• Permanent change in the sequence of DNA,
causing change in the structure or function of a
single gene
Account for 8% of all human malformations
• Dominant mutation
If a mutant gene produces an abnormality
in a single dose or single allele
Eg. Achondroplasia
112

• Recessive mutation
• both alleles are abnormal
• Adrenal hyperplasia and microcephaly,

Environmental Factors
• Although the human embryo is well protected in
the uterus, environmental agents-teratogens-may
cause developmental disruptions after maternal
exposure to them .
113

A teratogen is any agent that can produce a congenital
anomaly or increase the incidence of an anomaly in the
population.
Environmental factors, such as infec-tion and drugs,
may simulate genetic conditions, e.g., when two or
more children of normal parents are affected.

There are various type of teratogens
 Drugs
 Chemicals
 Infectious agent
 Radiation

Teratogens Associated With Human Malformations
114

Teratogens ssociated With Human Malformations͙

Teratogens ssociated With Human Malformations͙
116

ANOMALIES CAUSED BY MULTIFACTORIAL INHERITANCE
• Many common birth defects (e.g., cleft lip with or
without cleft palate) have familial distributions
consistent with multifactorial inheritance .
113

• Multifactorial inheritance may be represented
by a model in which "liability" to a disorder is a
continuous variable determined by a
combination of genetic and environmental
factors, with a developmental threshold dividing
individuals with the anomaly from those without
it .

Multifactorial traits are often single major
anomalies, such as cleft lip, isolated cleft palate,
neural tube defects (e.g., meroencephaly, spina
bifida cystica), pyloric stenosis, and congenital
dislocation of the hip.

• Some of these anomalies may also occur as part of
the phenotype in syndromes determined by single-
gene inheritance, chromosome abnormality, or an
environmental teratogen.
• The recurrence risks used for genetic counseling of
families having birth defects determined by
multifactorial inheritance are empirical risks based
on the frequency of the anomaly in the general
population and in different categories of relatives.

• In individual families, such estimates may be
inaccurate because they are usually averages for
the population rather than precise probabilities
for the individual family

• Other congenital anomalies, such as,
congenital suprarenal (adrenal) hyperplasia
and microcephaly, are attributed to autosomal
recessive inheritance.
• Autosomal recessive genes manifest
themselves only when homozygous; as a
consequence, many carriers of these genes
(heterozygous persons) remain undetected

Developmental Signaling Pathways
• Normal embryogenesis is regulated by several
complex signaling cascades .
• Mutations or alterations in any of these
signaling pathways can lead to birth defects.
• Many signaling pathways are cell autonomous
and only alter the differentiation of that
particular cell, as seen in proteins produced by
HOX A and HOX D gene clusters (in which
mutations lead to a variety of limb defects).
•

• Other transcriptional factors act by
influencing the pattern of gene expression of
other adjacent cells.
• These short-range signal controls can act as
simple on-off switches (paracrine signals);
others, termed morphogens, elicit many
responses depending on their level of
expression with other cells

• One such developmental signaling pathway is
initiated by the secreted protein called sonic
hedgehog (Shh) that sets off a chain of events in
target cells, resulting in activation and repression
of target cells by transcription factors in the Gli
family.
• Perturbations in the regulation of the Shh-
Patched-Gli (Shh-Ptch-Gli) pathway leads to
several human diseases including some cancers
and birth defects

References;
 Medical embryology,9th ed
 The developing human ,clinically oriented͙
emb.11th ed
 Langman embryology-11th ed
 Broad review series embryology
116

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