“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
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
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,
What happens next to the embryo, is very
EMBRY O’
In My mother’s womb…..
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)
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
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
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
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
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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
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
1. lacunae
2. endometrium
3. syncytiotrophoblast
4. cyto-trophoblast
5. surface epithelium of the endometrium
6. epiblast
7. amniotic cavity
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
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
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
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
1. Primitive Groove 2. Epiblast
3. Extraembryonic mesoderm 4. Hypoblast
5. Invading epiblast cells forming intra-embryonic mesoderm
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.
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
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
Mnemonic:
Primitive streak, Midline groove of Epiblast
cells, forms Mesoderm, Migrates all directions, Trilaminar disc forms
Prime Ministers of England Meet Many
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
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
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
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
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
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
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,
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
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
•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
Describe the difference between the chorionic
villi types?
What are the three layers of the trilaminar
disc?
•Chromosomal abnormalities may be
Numerical Abnormalities
•The normal human somatic cell contains 46
chromosomes.
•The normal gamete contains 23.
Normal somatic cells are diploid, or 2
n
. 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
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
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
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
•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
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
•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
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
