EMBRYOLOGY

FROM FERTILIZATION TO BIRTH

Recommended
reading:

Campbell Biology (11th Langmans’s Medical

Edition); Embryology, 11th ed.
Chapter 47: Animal
Development
 Stages of embryonic development:

• Progenesis – includes Spermatogenesis and

Oogenesis .
• Fertilization.
• Cleavage and the blastula formation.
• Gastrulation
• Neurulation and organogenesis.
Sex cell (haploid cell):
Spermatozoon (spermatozoa) = sperm cell
Ovum = Egg cell
MORPHOLOGY OF SPERMATOZOON

Head
Neck
Middle section
Tail
 Head
It has a compact nucleus with only chromatic substance and is
surrounded by only a thin rim of cytoplasm.

Above the nucleus lies a cap-like structure called the acrosome, formed
by modification of the Golgi body and which secretes enzyme spermlysin
(hyaluronidase, corona-penetrating enzyme, aerosin.)

Neck
It is the smallest part and has a proximal and distal centriole.
The proximal centriole enters into the egg during fertilisation and starts the first
cleavage division of the egg, which has no centriole.
The distal centriole gives rise to axial filament which forms the tail
 Middle section
It has 75-100 spirals of mitochondria surrounding axial filament in
the cytoplasm. It provides motility, and hence is called the
powerhouse of the sperm.

Tail
It is the longest part having axial filament surrounded by cytoplasm
and plasma membrane, but at the posterior end axial filament is naked.
 head
neck acrosome

tail

nucleus

Spermatozoa of guinea
pig.
Acrosome
Spermatozoa in other organisms
 OOCYTE MORPHOLOGY

Memrane complex:
plasma membrane
Zona pellucida
Ooplasm: yolk
mitochondria
cortical granules
The human ovum measures
approximately 0.12 mm in diameter Nucleus with nucleolus
 Zona pellucada
Corona radiata
Zona pellucida
(ZP-1, -2, and -3)
Cortical granules

The zona pellucida is a glycoprotein layer

surrounding the plasma membrane of
mammalian oocytes.

ZP3 allows species-specific sperm binding

ZP2 mediates subsequent sperm binding
ZP1 cross-links ZP2 and ZP3.
 Cortical granules
specialized secretory vesicles located within the egg's cortex
(the region directly below the plasma membrane).
The cortical granules contain proteases, peroxidases, and
glycozaminoglycans

The image shows oocyte that has

been stained to show cortical
granules (all the small red dots).
In this preparation, genomic DNA in
the metaphase plate of the secondary
oocyte (top right) appears bluish-
white.
Cortical granules
Follicle cells
• Mammalian egg contain only a tiny amount of the nutritive yolk, for
nourishing the embryo in the early stages of its development only.
• In contrast, bird eggs contain enough to supply the chick with
nutriment throughout the whole period of incubation

Egg size and yolk

Microlecithal eggs - simple with little yolk

(In placental mammals, sponge, lancelet)
Mesolecithal - medium-sized eggs with
some yolk (frog, snails)
Macrolecithal - large eggs with a large
concentrated yolk (cartilaginous fish,
reptiles, birds, and monotreme mammals).
 Abnormal gametes
Two egg cell Trinucleated
in follicle egg cell
A. One ovarian follicle contains two or three
primary oocytes. Although these oocytes may
give rise to twins or triplets, they usually
degenerate before reaching maturity.
B. One primary oocyte contains two or even
three nuclei. Such binucleated or trinucleated
oocytes die before reaching maturity
Different form of spermatozoa
In contrast to atypical oocytes,
abnormal sperm are seen frequently,
and up to 10 % of all spermatozoa have
observable defects. The head or the
tail may be giants or dwarfs, and
sometimes, they are joined. Sperm with
morphologic abnormalites lack normal
motility and probably do not fertilize
oocytes
 Stages of embryonic development:

• Progenesis – includes Spermatogenesis and

Oogenesis .
• Fertilization.
• Cleavage and the blastula formation.
• Gastrulation
• Neurulation and organogenesis.
Progenesis – includes formation of spermatozoa
and oocytes - male and female germ cells
Spermatogenesis – spermatozoa
development - is maintained in the
seminiferous tubules of testes

Oogenesis – oocyte
production - is maintained
within the ovarian follicles
 Meiosis is a specialized type of cell devision that reduces the
chromosome number by half, creating four haploid cell, each
genetically distinct from the parent cell that gave rise to them

Errors in meiosis resulting in aneuploidy are the leading known

cause of miscarriage and the most frequent genetic cause of
developmental disabilities
 Meiosis
• Meiosis I As in mitosis, male and female germ cells
(spermatocytes and primary oocytes) at the beginning
prophase I of meiosis I replícate their DNA so that each of the 46
metaphase I chromosomes is duplicated into sister chromatids.
anaphase I In contrast to mitosis, however, homologous
telophase I chromosomes then align themselves in pairs, a process
• Meiosis II called synapsis.

prophase II Homologous pairs then separate into two daughter cells,

metaphase II thereby reducing the chromosome number from diploid to
haploid.
anaphase II
telophase II Shortly thereafter, meiosis II separates sister chromatids.
Each gamete then contains 23 chromosomes.
Before meiosis begins, during S phase the DNA of each chromosome is
replicated so that it consists of two identical sister chromatids, which
remain held together through sister chromatid cohesion.

Meiosis I segregates homologous chromosomes, which are joined as

tetrad, producing two cells which each contain chromatid pairs
PROPHASE I
• Prophase I is typically the longest phase of meiosis.
• During prophase I, homologous chromosomes pair and
exchange DNA (homologous recombination).
• This results in chromosomal crossover. Crossovers, critical
events in meiosis I, are the interchange of chromatid
segments between paired homologous chromosomes
• The new combinations of DNA created are a significant source
of genetic variation.
• The paired and replicated chromosomes are called bivalents
or tetrads, which have two chromosomes and four chromatids,
with one chromosome coming from each parent.
• The process of pairing the homologous chromosomes is called
synapsis. At this stage, non-sister chromatids may cross-over
at points called chiasmata.
 PROPHASE I
1. Leptotene
Each chromosomes consisting of two sister chromatids.
The two sister chromatids closely associate and are visible.
During leptotene, lateral elements of the synaptonemal complex
assemble.
Leptotene is of very short duration and progressive
condensation and coiling of chromosome fibers takes place.
 PROPHASE I
2. Zygotene occurs as the chromosomes approximately line up
with each other into homologous chromosome pairs.
At this stage, the synapsis (pairing/coming together) of
homologous chromosomes takes place, facilitated by assembly
of central element of the synaptonemal complex (zipper-like
fashion).
The paired chromosomes are called bivalent or tetrad
chromosomes.
 PROPHASE I
3. Pachytene
At this point a tetrad of the chromosomes has formed known as a
bivalent.
Homologous recombination, including chromosomal crossover
(crossing over), occurs.
Nonsister chromatids of homologous chromosomes may
exchange segments over regions of homology. At the sites
where exchange happens, chiasmata form.
The exchange of information between the non-sister chromatids
results in a recombination of information; each chromosome
has the complete set of information it had before.
 PROPHASE I
4. Diplotene.
During the diplotene stage the synaptonemal complex degrades
and homologous chromosomes separate from one another a
little.
The chromosomes themselves uncoil a bit, allowing some
transcription of DNA.
Seperation will not takes place at chiasmata
Chiasmata are clearly visible as “X” shape
Chiasmata helps in holding homologous chromosomes until
anaphase I
 PROPHASE I
• Diakinesis
This the first point in meiosis where the four parts of the
tetrads are actually visible.
Homologous chromosomes separate further, and the
chiasmata terminalize. Making chiasmata clearly visible.
 Prophasa 1 meiosis.

For instance, the letters A, B, and C represent genes found at

particular spots on the chromosome, with capital and lowercase
letters for different forms, or alleles, of each gene.

The DNA is broken at the same spot on each homologue—here,

between genes B and C—and reconnected in a criss-cross
pattern so that the homologues exchange part of their DNA.
 Metaphase I
After crossing over, the spindle begins to capture chromosomes
and move them towards the center of the cell (metaphase plate).
Each chromosome attaches to microtubules from just one pole of
the spindle, and the two homologues of a pair bind to
microtubules from opposite poles.
So, during metaphase I, homologue pairs—not individual
chromosomes—line up at the metaphase plate for separation.
 Anaphase I
In anaphase I, the homologues are pulled apart and move apart
to opposite ends of the cell. The sister chromatids of each
chromosome, however, remain attached to one another and don't
come apart.

Telophase I
The chromosomes arrive at opposite poles of the cell.
Cytokinesis usually occurs at the same time as telophase I,
forming two daughter cells.
 Meiosis II
Cells move from meiosis I to meiosis II without copying their DNA.
Meiosis II is a shorter and simpler process than meiosis I
The cells that enter meiosis II are the ones made in meiosis I.
These cells are haploid—have just one chromosome from each
homologue pair—but their chromosomes still consist of two
sister chromatids.
In meiosis II, the sister chromatids separate, making haploid cells
with non-duplicated chromosomes.
• During prophase II, chromosomes condense and the nuclear
envelope breaks down. The centrosomes move apart, the
spindle forms between them, and the spindle microtubules
begin to capture chromosomes.
• In metaphase II, the chromosomes line up along the
metaphase plate.
• In anaphase II, the sister chromatids separate and are pulled
towards opposite poles of the cell.
• In telophase II, nuclear membranes form around each set of
chromosomes, and the chromosomes decondense.
• Cytokinesis splits the chromosome sets into new cells, forming
the final products of meiosis: four haploid cells in which each
chromosome has just one chromatid.
 Meiosis

Meioso consists of two

consecutive divisions
Meiosis
Birth Defects and Spontaneous Abortions:
Chromosomal and Genetic Factors
Chromosomal abnormalitíes, which may be
numerical or structural, are important causes of
birth defects and spontaneous abortions.
It is estimated that 50% of conceptions end in
spontaneous abortion and that 50% of these
abortuses have major chromosomal
abnormalities.
Thus, approximately 25% of conceptuses have a
major chromosomal defect. The most common
chromosomal abnormalities in abortuses are 45,
X (Turner syndrome), triploidy, and trisomy 16.
The normal human somatic cell contains 46 chromosomes; the normal
gamete contains 23.
Normal somatic cells are diploid - 2n; normal gametes are hapioid - n.
Eupioid refers to any exact múltiple of n [e.g., diploid or triploid]
Aneupioid refers to any chromosome number that is not eupioid;
it is usually applied when an extra chromosome is present (trisomy] or
when one is missing (monosomy)
• 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)
 Phenotypes of these aneuploidies range from severe developmental
disorders to asymptomatic.

Trisomy 21 [Down Syndrome] is caused by an extra copy

of chromosome 21
• Turner syndrome, with a 45, X karyotype, Is the only
monosomy compatible with life. Even then, 98% of all fetuses
with the syndrome are spontaneously aborted.-

• Triple X Syndrome. Patients with triple X syndrome (47,

XXX) often go undiagnosed because of their mildl physical
features.

• trisomy of chromosome 21

• Patau syndrome – trisomy of chromosome 13

• Edwards syndrome – trisomy of chromosome 18

• Klinefelter syndrome – extra X chromosomes in males – i.e.

XXY, XXXY, XXXXY, etc.

• XYY syndrome – an extra Y chromosome in males.

 Spermatogenesis In the seminiferous tubules

Spermatogenesis, which begins at puberty,

includes all of the events by which spermatogo-
nia are transformed into spermatozoa.

At regular intervals, spermatogonia cells undergo

of mitotic divisions to form clones of cells and then
divide to form primary spermatocytes

Primary spermatocytes then enter a prolonged

prophase (22 days) and for mation of secondary
spermatocytes.

During the second meiotic división, these cells

immediately begin to form haploid spermatids

The series of changes resulting in the trans-

formation of spermatids into spermatozoa is
spermiogenesis.
Supporting cells of the surface epithelium In the testis seminiferous tubules
are Sertoli cells

In humans, the time required for a spermatogonium to develop

into a mature spermatozoon is approximately 74 days, and
approximately 300 million sperm cells are produced daily.
FIGURE 21-7 Copyright © McGraw-Hill Companies
FIGURE 21-6 Copyright © McGraw-Hill Companies
FIGURE 21-5 Copyright © McGraw-Hill Companies
FIGURE 21-8 Copyright © McGraw-Hill Companies
 Oogenesis
oogenesis begins before birth;

After repeated mitotic divisions, some of

oogonia arrested in prophase of meiosis I
form primary oocytes.
By the seventh month, many oogonia have
become atretic, and only primary oocytes
remain

The primary oocyte remains in prophase

of the first meiotic división until puberty

In a puberty, once a month, a surge in luteinizing hormone (LH) stimulates

preovulatory growth: Meiosis I is completed, and secondary oocyte and
polar body are formed.
Then, the secondary oocyte is arrested in metaphase of meiosis II
approximately 3 hours before ovulation and will not complete this cell división
until fertilization.
Most mammals ovulate an "egg" that has
matured into a secondary oocyte;
it is always the secondary oocyte that is
fertilized.
FIGURE 22-1 Copyright © McGraw-Hill Companies
FIGURE 22-2 Copyright © McGraw-Hill Companies
 Schematic sequence of complete follicular development

Preantral phase: Formation and beginning of growth and activation of

primordial follicles and growth of primary and secondary follicles.
Antral phase: formation of tertiary follicle (antral-filled follicular fluid
cavity).
Oogonia develop from a primordial germ cell and differentiates into an
oocyte in the ovary. Primordial follicle has a single layer of flattened
granulosa cells.
Primary follicle has a single layer of cuboidal granulosa cells.
Secondary follicle has two or more layers of cuboidal granulosa cells
and a small number of theca cells.
All the preantral follicles have a primary oocyte.
 Schematic sequence of complete follicular development

Tertiary follicle has: several granulosa cell layers, theca cells,

and primary oocyte and is characterized by an antral cavity which
contains follicular fluid.
Preovulatory or also called as Graafian follicle is the last stage of
follicle development; these follicles are larger, have more antral
fluid and contain a secondary oocyte. Follicular fluid is a plasma
exudate conditioned by secretory products from the granulosa cells
and oocyte.
FIGURE 22-3 Copyright © McGraw-Hill Companies
FIGURE 22-4 Copyright © McGraw-Hill Companies
FIGURE 22-5 Copyright © McGraw-Hill Companies
FIGURE 22-6 Copyright © McGraw-Hill Companies
FIGURE 22-7 Copyright © McGraw-Hill Companies
FIGURE 22-8 Copyright © McGraw-Hill Companies
FIGURE 22-10 Copyright © McGraw-Hill Companies
• By the end of the follicular phase of the thirteenth day of the
menstrual cycle, the preovulatory follicle will develop an
opening, and excrete the oocyte with a complement of cumulus
cells in a process called ovulation.
• The oocyte is technically still a secondary oocyte, suspended
in the metaphase II of meiosis.
FIGURE 22-11 Copyright © McGraw-Hill Companies
FIGURE 22-17 Copyright © McGraw-Hill Companies
 Follicle Maturation and Ovulation
Oocytes
~2 million at birth
~40,000 at puberty
~400 ovulated over lifetime

Leutinizing Hormone surge

(from pituitary gland)
causes changes in tissues
and within follicle:
• Swelling within follicle due to
increased hyaluronan
• Matrix metalloproteinases
degrade surrounding tissue
causing rupture of follicle

Egg and surrounding cells

(corona radiata) ejected into
peritoneum
Corona radiata provides bulk to
facilitate capture of egg.
Transport through the oviduct
At around the midpoint of the
menstrual cycle (~day 14), a
single egg is ovulated and
swept into the oviduct.
Fertilization usually occurs
in the ampulla of the oviduct
within 24 hrs. of ovulation.
Series of cleavage and
differentiation events results
in the formation of a
blastocyst by the 4th
embryonic day.
Inner cell mass generates
embryonic tissues
Outer trophectoderm
generates placental tissues

Implantation into the uterine

wall occurs ~6th embryonic
day (day 20 of the menstrual
cycle)
Ovulation
 Stages of embryonic development:

• Progenesis – includes Spermatogenesis and

Oogenesis .
• Fertilization.
• Cleavage and the blastula formation.
• Gastrulation
• Neurulation and organogenesis.
 FERTILIZATION

• Fusion of a spermatozoon with oocyte resulting in

formation of one-cell embryo – zygote

• Fertilization in most of the cases occurs within the

ampullary region of the uterine tube on days 14-15 of
ovarian-menstrual cycle and insemination with sperm

• Fertilization is accounted as the first day of

embryogenesis
 MAIN EVENTS DURING
FERTILIZATION
• Capacitation
• Acrosomal reaction
• Penetration of corona radiata and zona
pellucida
• Fusion of the oocyte and sperm cell
membranes
• Cortical and zona pellucida reactions
• Resumption of 2nd meiotic division
• Metabolic activation of the egg
• Restoration of diploid number of chromosomes
 Capacitation
The sperm must undergo capacitation in the female's
reproductive tract, which increases its motility and destabilizes
its membrane, preparing it for the acrosome reaction, the
enzymatic penetration of the egg's tough membrane, the zona
pellucida, which surrounds the oocyte.
Glycoprotein coat and plasma proteins are removed from the
plasma membrane that overlies the acrosomal región of the
sperm.
Only capacitated sperm can pass through the corona cells and
undergo the acrosome reaction
 Penetration of the Corona Radiata

Of the 200 to 300 million spermatozoa normally

depositad in the female genital tract,
only 300 to 500 reach the site of fertilization.
Only one of these fertilizes the egg. It is thought that the others
aid the fertilizing sperm in penetrating the barriers protecting
the female gamete.
Capacitated sperm pass freely through corona cells
Penetration of the Zona Pellucida

The zona is a glycoprotein shell surrounding

the egg that facilitates and maintains sperm
binding and induces the acrosomal reaction.

Both binding and the acrosome reaction are mediated by

the ligand ZP3, a zona protein.
Release of acrosomal enzymes (acrosin) allows sperm to
penetrate the zona, thereby coming in contact with the
plasma membrane of the oocyte
 Acrosomal Reaction

sperm bind to ZP3 proteins in the zona pellucida;

this initiates the release of enzymes (acrosin) from the
sperm allowing it to burrow through the zona pellucida.
 Cortical reaction
Permeability of the zona pellucida changes when the head of the
sperm comes in contact with the oocyte surface.
This contact results in release of lysosomal enzymes from cortical
granules lining the plasma membrane of the oocyte.
In turn, these enzymes alter properties of the zona pellucida to
prevent sperm penetration and inactivate species-specific receptor
sites for spermatozoa on the zona surface.
Other spermatozoa have been found embedded in the zona pellucida,
but only one seems to be able to penetrate the oocyte
This so-called cortical reaction prevents other sperm
from fertilizing the egg - prevention of polyspermy

Cortical granule
enzymes digest ZP
proteins so other sperm
can no longer bind.

Hyaluronic acid and

other proteoglycans are
also released that
become hydrated and
swell, thus pushing the
other sperm away.
Fertilization is a multi-step process whereby multiple sperm bind to the
corona radiata, but only a single sperm usually fertilizes the egg

After adhesion, the plasma membranes of the sperm and egg fuse
Fertilization

Meiosis II complete

Formation of male and

female pronuclei

Decondensation of male
chromosomes

Fusion of pronuclei

Zygote
Fertilized egg (zygote)

Fertilized egg
2 polar bodies
2 pronuclei

Day 1
0.1 mm
Abnormal zygotes
Fertilization
Fertilization
 The main results of fertilization:

• Restoration of the diploid number of chromosomes

• Determination of the sex of embryo

• Initiation of a cleavage