“It is not birth, marriage or death but

gastrulation that is the most important time in

your life” Lewis Walpert 1986
 It is the time that elapses between
fertilisation and the birth of a new individual.
It is about 9 calendar months.
 The intra-uterine life of the individual is
divided into 3 stages.
 Stage1- Germinal Period- 1st 2 weeks
 Stage 2- Embryonic Period- 2nd week to 3rd
month
 Stage 3- Foetal Period-3rd month to 9th
month
 Fusion of the male and female gametes happens in the Fallopian tube
 Egg complex is surrounded by cells called the Corona Radiata and a
Zona Pellucida
 Radiata is penetrated by sperm and reaches the ZP
 Three glycoproteins make up the ZP, 1, 2 and 3
 Initially, the sperm binds to ZP3
 Liberation of enzymes found in sperm sac called acrosome
 In the acrosome are acid proteinase, collagenase, acrosin amongst
others
 Zona Pellucida binding stimulates this release of enzymes from the sac
 Acrosomal reation is the name given to this process and it helps the
sperm to get through the ZP.
 Tail of the sperm also propels it forward
 Influx of Calcium into the sperm head assist this process
 One plasma membrane is formed by fusing the sperm and egg
membranes
 Nuclei (haploid/pronuceli) of both join up to form diploid egg.
 Definition: The fusion of male and female
gametes
 Site: Lateral 1/3 of the Fallopian tube
 Mechanism: The fertilising sperm pierces the
corona radiata and Zona Pellucida. The head
detaches from the rest of the sperm and
forms the male pronucleus which contains
half the number of chromosomes. The
nucleus of the ovum is also haploid and both
fuse to form a dilpoid zygote.
 There is a ball covered in velcro and a needle and
syringe which is to be inserted into the balloon.
The ball is like the ovum and the needle is the
sperm and the velcro is the Zona Pellucida.
 The ball has been on the floor for a long time
and stuck to the velcro is a lot of fluff from the
rug (fluff is the corona radiata). We need to
insert the needle through the velcro and into the
balloon. So we need to remove the fluff first
(corona radiata). The needle needs to then get
through the velcro (the ZP) before it gets to the
balloon. It attaches to the velcro first (to ZP3) and
then penetrates it. In the syringe attached to the
needle is a potent acid. We're going to use the
syringe and needle to release some acid to
dissolve the velcro (the acid in the syringe is like
the acrosomal sac contents), so we can penetrate
the ball.
 Describe the Essential Steps in fertilisation.
 Describe cellular events in fertilisation.

Buzz Words:
 Zona Pellucida, Corona Radiata, ZP3,
Acrosomal Reaction, Fusion, Pro-nuceli
 What happens next to the embryo, is very
interesting and fast paced.
EMBRY O’
In My mother’s womb…..
THE AUTOBIOGRAPHY
 Definition: a series of mitotic divisions
occurring in the zygote. Each cell that results
is called a blastomere.
 Site: these divisions occur in the zygote as it
passes in the fallopian tube to reach the
uterine cavity.
 The 2 cell stage appears at 30 hours after fertilisation
 The 4 cell stage appears at around 45 hours after fertilisation
 The Morula is the 12-16 cell stage and appears about 3rd day
 The cells become arranged into an inner cell mass in the
centre and an outer cell mass in the periphery
 The Blastocyst develops on the 4th day
 As the cells of the morula continue to divide, fluid from the
uterine cavity enters the spaces between the cells.
 These fluid filled spaces join together to form one large cavity
called a blastocele and the morula is now called a
blastocyst.(the Zona Pellucida disappears completely at day 4)
 On the 6th day
 The cells of the outer cell mass form the
trophoblast- will form foetal membranes later
on
 The cells of the inner cell mass become
located at one pole- called the embryonic
pole (the opposite pole is called the
abembryonic pole)

 The blastocyst attaches to the endometrium

at 5-6 days after fertilisation.
 Definition: It is the penetration of the
blastocyst into the superficial compact layer
of the endometrium.
 Time: Begins day6 or 7 and ends by day 11 or
12.
 Site: endometrium of the posterior wall of the
fundus of the uterus
 The blastocyst becomes attached to the
endometrium by its embryonic pole
 The trophoblast cells covering the embryonic
pole erode the epithelium of the
endometrium (possibly by enzymatic
action)to allow the blastocyst to penetrate
through the defect.
 After complete embedding of the blastocyst,
the penetration defect is closed by a fibrin
clot.
 Implantation is completed by growth of the
epithelium to cover the defect.
 Sixth/Seventh day
 Fundus of Uterus
 Embryonic pole attaches
 Trophoblasts erode endometrium
 Penetration defect formed
 Blastocyst enters
 Embeds completely
 Closed by a clot
 Intact epithelium again

 Sad Forgotten Emos Try Partying But Eat Carrots

Instead
  The following things happen:
1. Implantation: is complete (11th/12th day)
2. Trophoblast differentiates into TWO layers
(syncytio-trophoblast and cytotrophoblast)
3. Inner cell mass becomes TWO layers (called
bilaminar germ disc and composed of
Ectodermal layer and Endodermal layer)
4. TWO cavities are formed (amniotic cavity and the
yolk sac)
 NB) there is a rapid rate of growth in the second
week compared to the first week
 The blastocyst is still partially embedded in the
endometrium
 Inner cell mass forms 2 layers- an inner ENDODERM
(hypoblast) (small polygonal cells) and an outer
ECTODERM (epiblast) (tall columnar cells).
 The trophoblast starts to differentiate into 2 layers:
 Outer dark zone without cell boundaries called the
SYNCYTIOTROPHOBLAST and an inner pale zone with
clear boundaries called CYTOTROPHOBLAST.
 An Amniotic Cavity starts to be formed : small clefts
appear between the ectodermal cells and the
trophoblastthe clefts join each other to form the
amniotic cavity. The cytotrophoblast develops a layer
of cells called amnioblasts which form the roof of the
amniotic cavity, while the floor is formed by the
epiblast or ectoderm.
1. lacunae
2. endometrium
3. syncytiotrophoblast
4. cyto-trophoblast
5. surface epithelium of the endometrium
6. epiblast
7. amniotic cavity
8. hypoblast
 The blastocyst becomes more deeply implanted
and the fibrin clot covers the penetration defect.
 The trophoblast becomes fully differentiated into
cyto and syncytio-trophoblast.
 Spaces called lacunae appear in the syncytio-
trophoblast.
 The amniotic cavity becomes larger
 A second cavity forms called the Primary Yolk Sac
at the ventral aspect of the embryonic disc. The
Primary Yolk sac is the new name for the old
blastocyst cavity. Its roof is formed by the
endodermal layer of the hypoblast and the rest of
its lining is called Heuser's membrane.
 The blastocyst is completely embedded by
now
 Lacunae in the syncytio-trophoblast formed
earlier start communicating with each other
to form larger spaces. This is a primitive
maternal foetal circulation.
 Formation of the extra-embryonic mesoderm:
 cells of inner surface of the cyto-trophoblast
form a loose tissue called extra-embryonic
mesoderm
1. syncytiotrophoblast
2. lacunae
3. surface epithelium of the endometrium
4. fibrin clot
5. epiblast
6. amniotic cavity
7. hypoblast
8. primary chorionic villi/cytotrophoblast
9. primary yolk sac
 Cavities are formed inside the extra-
embryonic mesoderm. These cavities fuse
together to form the extra-embryonic
coelom. However, the coelom doesn't replace
the mesoderm completely, rather it divides it
into two, SOMATOPLEURE which lines the
cyto-trophoblast and the splanchnopleure
which covers the yolk sac.
 NB) The connecting stalk is a mass of
mesoderm connecting the roof of the
amniotic cavity with the trophoblast.
imagine the extra-embryonic mesoderm is like
the a dried up oxbow lake and the yolk sac and
amniotic cavity and bilaminar germ disc is an
island in the middle. When the water flows in the
rainy season. The lake has two river banks or two
lake edges on either side. The water is like the
extra-embryonic coelom and the banks on either
side are the somatopleure (on the outside- has
an O) and splanchnopleure (on the inside, has an
N). There is a bridge connecting the island to the
outer edge/bank. This is the connecting stalk.
 1. secondary yolk sac
 2. remnants of the primary yolk
 3. amniotic cavity
 4. extra-embryonic coelom
 5. epiblast
 6. connecting stalk
 7. hypoblast
 8.syncytiotrophoblast
 9. lacunae
 10. somatopleure
 11. splanchnopleure
 The most prominent changes are the
appearance of primary chorionic villi as
follows:
 Parts of the cytotrophoblast at the embryonic
pole project into the syncytiotrophoblast
forming primary chorionic villi, surrounded
by lacunae.

 The primary yolk sac gets smaller and gets
pinched off and is now called the secondary
yolk sac.
 Week 2 of Pregnancy:
 2 cavities
 2 germ cell layers
 2 trophoblast layers
Summary:

 Changes in the embryonic disc

1. Formation of the intra-embryonic mesoderm-
now a TRILAMINAR germ disc
2. Formation of the notochord- which is a
temporary supporting structure to the
embryonic disc
 Changes to the trophoblast (chorion): 3 types of
chorionic villi form and cover the whole surface
of the chorionic vesicle.
1. Primitive groove
2. Primitive pit
3. Primitive node
4. Oropharyngeal membrane/Prochordal plate
5. Cardiogenic plate
6. Sectional edge of amniotic membrane
7. Mesoderm
8. Endoderm
9. Future cloacal membrane
1. Primitive Groove
2. Epiblast
3. Extraembryonic mesoderm
4. Hypoblast
5. Invading epiblast cells
forming intra-embryonic
mesoderm
6. Hypoblast again
 Formation of the primitive streak:

 At the beginning of the third week,

ectodermal cells in the caudal part of the
bilaminar germ disc migrate to the midline
forming a primitive streak (a narrow midline
groove)- basically the cells of the epiblast
migrate downwards forming a groove.
These cells separate from the epiblast (now
called ectoderm) and migrate in all directions.
This new layer of cells is called the intra-
embryonic mesoderm. There is an area in the
cranial end that it doesn’t migrate to, that is the
propchordal plate and an area called the cloacal
membrane, behind the primitive streak. These
areas remain BILAMINAR.
Why?
 Because mesoderm forms vascular tissue.
These bilaminar areas do not have mesoderm
so without a blood supply they will break
down. This is important as these areas need
to break down to form contact with the
external environment:
 Prochordal plate  buccopharyngeal opening
 Cloacal membrane  anus
Pillow and Pillow Cover.

The two pieces of material sewn together to form

the pillow cover are the epiblast (ectoderm) and
hypoblast (endoderm). When I want to stuff the
pillow into the pillow cover, there needs to be an
opening, yeh? That opening is like the primitive
streak. When I stuff the pillow I make sure the
whole of the pillow case is encased with pillow. The
stuffing is the mesoderm, the pillow cover
represents the ectoderm and mesoderm.
Mnemonic:

 Primitive streak, Midline groove of Epiblast

cells, forms Mesoderm, Migrates all
directions, Trilaminar disc forms

 Prime Ministers of England Meet Many

Troubles
This whole process of mesoderm formation is
called GASTRULATION
Mesoderm components MESODERM:
 Mesothelium (peritoneal, pleural, pericardial)/
Muscle (striated, smooth, cardiac)
 Embryologic Spleen/ Soft tissue/ Serous linings/
Sarcoma/ Somite
 Osseous tissue/ Outer layer of suprarenal gland
(cortex)/ Ovaries
 Dura/ Ducts of genitalia
 Endothelium
 Renal Microglia
 Mesenchyme/ Male gonad
 There is a thickening of the ectoderm at the
cephalic end of the primitive streak and the
primitive node, remember, is where there is the
central depression with the slightly elevated area.

 The cells of this primitive node proliferate and
form a solid rod of cells called notochordal
process which grows in a cephalic direction
between the endoderm and ectoderm.

 Inside the notochordal process Is a small central
notochordal canal which passes from the
primitive pit anteriorly.
 The notochord is a bit like a hollow metal
pipe that passes through the pillow we talked
about earlier.
 The notochord gives the embryo structure
and helps it to define its axes.
Formation of the chorionic villi
 Primary chorionic villi: begin to appear by the
end of 2nd week at the embryonic pole of the
chorionic vesicle and increase in number by
the beginning of the 3rd week. Each primary
villus is made up of a central core of
cytotrophoblast and a covering layer of
syncytiotrophoblast.
 Secondary chorionic villi: by the beginning of
the 3rd week, cells from the extra-embryonic
mesoderm start to penetrate the primary
chorionic villi and forms secondary chorionic
villi. Each secondary chorionic villus is made
up of a central core of extra-embryonic
mesoderm, a middle zone of cytotrophoblast
and an outer zone of syncytiotrophoblast.
 Tertiary chorionic villi: by the end of the 3rd
week, a loop of afferent and efferent
capillaries appears in the mesodermal core of
the secondary chorionic villi. The afferent
one is connected to the umbilical artery and
the efferent one is connected to the umbilical
vein.
 Differentiation of the Intra-embryonic
mesoderm:
 The mesoderm is formed as a loose tissue
between the ectoderm and endoderm by day
17 on either end of the notochord.
 As development proceeds, 2 longitudinal
grooves appear in the mesoderm on either
side of the notochord, dividing it into 3 parts.
 Imagine 2 sheets of wood and a pipe between
them. The joiner cuts the each piece of wood
on either side into 3 parts.
 Paraxial mesoderm, on either side of the
notochord
 About 20th day, transverse grooves appear
dividing the paraxial mesoderm into somites
(blocks). The first pair form day 20. 3
additional ones form each day from 21st to
30th day i.e. by the end of 1st month, 30 or 31
pairs of somites are formed. B
 Day 30-40, rate has slowed and finally 42-44
pairs are formed.
 4 occipital, 8 cervical, 12 thoracic, 5 lumbar,
5 sacral and 8-10 coccygeal.
 By the end of the 4th week, the somites
differentiate, so each somite divides into 2
parts:
 A ventro-medial part called the sclerotome
(becomes mesenchyme, CT, bone cells)
 A dorso-lateral part called dermomyotome
(becomes skin and muscles).
 S- structures of the paraxial mesoderm
 O- occipital to coccygeal
 M- mesodermal tissue
 T-TWO parts- ventromedial and dorsolateral
 E- embryo age can be estimated from
number of somites
 This tissue, which temporarily connects the
paraxial mesoderm with the lateral plate

 In the cervical and upper thoracicregions it

forms segmentally arranged cell clusters (the
future nephrotomes), whereas more caudally
it forms an unsegmented dmass of tissue
known as the nephrogenic cord. From this
partly segmented, partly unsegmented
intermediate mesoderm developesthe
excretory units of the urinary system.
 Divisions of the lateral plate mesoderm:

 Cavities form in the lat. Plate mesoderm that

divide it up into 2 layers:
 Somatic mesoderm: apposed to the ectoderm
(forms CT and muscles and supportive
elements of the body wall)
 Splanchnic mesoderm: apposed to the
endoderm (forms pleura, pericardium,
peritoneum, smooth muscles, CV system)
 At the beginning of 3rd week ectoderm is oval
in shape
 Ectoderm, over notochord and prechordal
mesoderm, thickens to form neural
palate(process is NEURULATION)
 Process by which the neural tube is formed
(future brain)
 Neural tube is formed and closed by the end
of week 4, there are openings cranially and
caudally called neuropores.
 Neural crest cells form as the neural tube
closes
 Neural crest cells form peripheral ganglia
(sensory and autonomic and Schwann cells)
 Cells thicken in the ectoderm overlying the
notochord (cranio-caudally)
 Cells at the periphery of this edge form neural
folds which elevate and fuse together in the
middle forming a neural tube.
 As it fuses some cells break away- neural crest
cells. These cells migrate to the mesoderm along
specific pathways to form peripheral ganglia.
 The neuropores at either end must close, if the
posterior one doesn’t close- SPINA BIFIDA. If the
anterior one doesn’t close- ANENCEPHALY.
 Occulta
 Meningocoele
 Meningomyocoele

 Folic Acid important in preventing this.

Unknown mechanism of action but thought to
have an effect on cell division in the neural
tube.
 •During the 2nd month of development, the
age of the embryo is then indicated as the
crown-rump (CR) length and expressed in
millimeters.
 •Formation of the limbs, face, ears, nose, and
eyes.•By the beginning of the 5th week, the
hind and forefingers appear as paddle-
shaped buds.
 •Ossification in the long bones begin by the
end of embryonic period (7th week).
 Describe the difference between the chorionic
villi types?
 What are the three layers of the trilaminar
disc?
 Describe the formation of the neural tube?
 •Chromosomal abnormalities may be
numerical or structural.
 Numerical Abnormalities
 •The normal human somatic cell contains 46
chromosomes.
 •The normal gamete contains 23.

 Normal somatic cells are diploid, or 2n.

 Normal gametes are haploid.
 Aneuploid refers to any chromosome number
that is not euploid.
 •it is usually applied when an extra
chromosome is present (trisomy) or when one
is missing (monosomy).
 •Abnormalities in chromosome number may
originate during meiotic or mitotic divisions.
 Sometimes, however, separation does not
occur (nondisjunction), and both members of
a pair move into one cell.
 •As a result of nondisjunction of the
chromosomes, one cell receives 24
chromosomes, and the other receives 22
instead of the normal 23.
 When, at fertilization, a gamete having 23
chromosomes fuses with a gamete having 24 or
22 chromosomes, the result is an individual with
either 47 chromosomes (trisomy) or 45
chromosomes (monosomy).
 •Nondisjunction, which occurs during either the
first or the second meiotic division of the germ
cells, may involve the autosomes or sex
chromosomes.
 •In women, the incidence of chromosomal
abnormalities, including nondisjunction,
increases with age, especially at 35 years and
older.
 Occasionally nondisjunction occurs during
mitosis (mitotic nondisjunction) in an
embryonic cell during the earliest cell
divisions.
 •Such conditions produce mosaicism, with
some cells having an abnormal chromosome
number and others being normal.
 •Affected individuals may exhibit few or
many of the characteristics of a particular
syndrome, depending on the number of cells
involved and their distribution.
 Sometimes chromosomes break, and pieces
of one chromosome attach to another.
 •Such translocations may be balanced, in
which case breakage and reunion occur
between two chromosomes but no critical
genetic material is lost and individuals are
normal.
 •Or they may be unbalanced, in which case
part of one chromosome is lost and an
altered phenotype is produced.
 For example, unbalanced translocations
between the long arms of chromosomes 14
and 21 during meiosis I or II produce
gametes with an extra copy of chromosome
21, one of the causes of Down syndrome.
 •Translocations are particularly common
between chromosomes 13, 14, 15, 21, and
22 because they cluster during meiosis.
 •Down syndrome is usually caused by an extra
copy of chromosome 21 (trisomy 21).
 •Features of children with Down syndrome
include growth retardation, varying degrees of
mental retardation, craniofacial abnormalities,
including upward slanting eyes, epicanthal folds,
flat facies, and small ears, cardiac defects, and
hypotonia.
 •These individuals also have relatively high
incidences of leukemia, infections, thyroid
dysfunction, and premature aging.
 •Furthermore, nearly all develop signs of
Alzheimer’s disease after age 35.
 In 95% of cases, the syndrome is caused by
trisomy 21 resulting from meiotic
nondisjunction, and in 75% of these
instances, nondisjunction occurs during
oocyte formation.
 •The incidence of Down syndrome is
approximately 1 in 2000 conceptuses for
women under age 25.
 •This risk increases with maternal age to 1 in
300 at age 35 and 1 in 100 at age 40.
 In approximately 4% of cases of Down
syndrome, there is an unbalanced
translocation between chromosome 21 and
chromosome 13, 14, or 15.
 •The final 1% are caused by mosaicism
resulting from mitotic nondisjunction.
 •These individuals have some cells with a
normal chromosome number and some that
are aneuploid.
 •They may exhibit few or many of the
characteristics of Down syndrome.
 •Patients with trisomy 18 show the following
features: mental retardation, congenital heart
defects, low-set ears, and flexion of fingers and
hands.
 •In addition, patients frequently show
micrognathia, renal anomalies, syndactyly, and
malformations of the skeletal system.
 •The incidence of this condition is approximately
1 in 5000 newborns.
 •Eighty-five percent are lost between 10 weeks
of gestation and term, whereas those born alive
usually die by age 2 months.
 •The main abnormalities of trisomy 13 are
mental retardation, holoprosencephaly,
congenital heart defects, deafness, cleft lip
and palate, and eye defects, such as
microphthalmia, anophthalmia, and
coloboma.
 •The incidence of this abnormality is
approximately 1 in 20,000 live births, and
over 90% of the infants die in the first month
after birth.
 •The clinical features of Klinefelter syndrome,
found only in males and usually detected at
puberty, are sterility, testicular atrophy,
hyalinization of the seminiferous tubules, and
usually gynecomastia.
 •The cells have 47 chromosomes with a sex
chromosomal complement of the XXY type,
and a sex chromatin body (Barr body) is
found in 80% of cases.
 The incidence is approximately 1 in 500 males.
 •Nondisjunction of the XX homologues is the
most common causative event.
 •Occasionally, patients with Klinefelter syndrome
have 48 chromosomes: 44 autosomes and four
sex chromosomes (XXXY).
 •Although mental retardation is not generally
part of the syndrome, the more X chromosomes
there are, the more likely there will be some
degree of mental impairment.
 •Turner syndrome, with a 45,X karyotype, is
the only monosomy compatible with life.
Although, 98% of all fetuses with the
syndrome are spontaneously aborted.
 •The survivals are female in appearance and
are characterized by the absence of ovaries
(gonadal dysgenesis) and short stature.
 •Other common associated abnormalities are
webbed neck, lymphedema of the
extremities, skeletal deformities, and a broad
chest with widely spaced nipples.
 Approximately 55% of affected women are
monosomic for the X and chromatin body
negative because of nondisjunction.
 •In 80% of these women, nondisjunction in
the male gamete is the cause.
 •In the remainder of women, structural
abnormalities of the X chromosome or mitotic
nondisjunction resulting in mosaicism are the
cause.
 Structural Abnormalities
 •They involve one or more chromosomes,
usually result from chromosome breakage.
 •Breaks are caused by environmental factors,
such as viruses, radiation, and drugs.
 •The result of breakage depends on what
happens to the broken pieces.
 •In some cases, the broken piece of a
chromosome is lost, and the infant with
partial deletion of a chromosome is
abnormal.
 A well-known syndrome, caused by partial
deletion of the short arm of chromosome 5,
is the cri-du-chat syndrome.
 •Such children have a catlike cry,
microcephaly, mental retardation, and
congenital heart disease.
 •Many other relatively rare syndromes are
known to result from a partial chromosome
loss.
 •Microdeletions, spanning only a few
contiguous genes, may result in
microdeletion syndrome or contiguous gene
syndrome.
 •An example of a microdeletion occurs on
the long arm of chromosome 15.
 •Inheriting the deletion on the maternal
chromosome results in Angelman syndrome.