Gametogenesis : Conversion of Germ

Cells into Male and Female Gametes

dr. Candys Libio

Primordial Germ Cells (PGCs)

Development of zygote begins with fertilization,

the process by which the male gamete, the
sperm, and the female gamete, the oocyte,
unite to give rise to a zygote.
Primordial Germ Cells

• Gametes are derived

from PGCs that are
formed in the epiblast
during the second
week, move through
the primitive streak
during gastrulation, and
migrate to the wall of
the yolk sac in 4th
week.
Primordial Germ Cells

• During the 4th week, primordial germ cells

begin to migrate from the yolk sac toward
the developing gonads, where they arrive
by the end of the 5th week.
• Mitotic divisions increase their number
during their migration and also when they
arrive in the gonad.
Primordial Germ Cells

In preparation for fertilization, both

male and female germ cells undergo
gametogenesis, which includes
meiosis to reduce the number of
chromosomes and cytodifferentiation
to complete their maturation.
The Chromosome Theory of Inheritance

• Humans have approximately 23,000 genes on

46 chromosomes that inherited from father
and the mother.

• In somatic cells, chromosomes appear as 23

homologous pairs to form the diploid number
of 46. There are 22 pairs of matching
chromosomes, the autosomes, and one pair
of sex chromosomes.
The Chromosome Theory of Inheritance

• If the sex pair is :

– XX  female
– XY  male

• One chromosome of each pair is derived from

the maternal gamete, the oocyte, and one from
the paternal gamete, the sperm.
• Thus, each gamete contains a haploid number
of 23 chromosomes, and the union of the
gametes at fertilization restores the diploid
number of 46.
Mitosis

• Mitosis is the process whereby one cell

divides, giving rise to two daughter cells
that are genetically identical to the parent
cell.

• Each daughter cell receives the complete

complement of 46 chromosomes. Before a
cell enters mitosis, each chromosome
replicates its DNA.
Mitosis

• During this replication phase, chromosomes

are extremely long, they are spread diffusely
through the nucleus.
• With the onset of mitosis, the chromosomes
begin to coil, contract, and condense; these
events mark the beginning of prophase.
• Each chromosome now consists of two
parallel subunits, chromatids, that are joined
at a narrow region common to both called the
centromere.
Mitosis

• Throughout prophase, the chromosomes

continue to condense, shorten, and
thicken (Fig. 2.3A), but only at
prometaphase do the chromatids become
distinguishable (Fig. 2.3B).

• During metaphase, the chromosomes line

up in the equatorial plane, and their
doubled structure is clearly visible (Fig.
2.3C).
Mitosis
• Each is attached by microtubules extending from
the centromere to the centriole, forming the mitotic
spindle.
• Soon, the centromere of each chromosome
divides, marking the beginning of anaphase,
followed by migration of chromatids to opposite
poles of the spindle.

• Finally, during telophase, chromosomes uncoil

and lengthen, the nuclear envelope reforms, and
the cytoplasm divides (Fig. 2.3 D-F) and each
daughter cell receives half of all doubled
chromosome material.
Mitosis
Meiosis

• Meiosis is the cell division that takes places in the

germ cells to generate male and female gametes,
sperm and egg cells.
• Meiosis required two cell divisions, meiosis I and
meiosis II, to reduce the number of chromosomes to
the haploid number of 23 (Fig. 2.4).

• As in mitosis, male and female germ cells

(spermatocytes and primary oocytes) at the beginning
of meiosis I replicate their DNA so that each of the 46
chromosomes is duplicated into sister chromatids.
Meiosis

• Homologous chromosomes then align

themselves in pairs, a process called synapsis.
• Homologous pairs then separate into two
daughter cells, thereby reducing the
chromosome number from diploid to haploid
• Shortly thereafter, meiosis II separates sister
chromatids. Each gamete then contains 23
chromosomes.
Crossover

• Crossovers, critical events in meiosis I, are the

interchange of chromatid segments between
paired homologous chromosomes (Fig. 2.4C).
• Segments of chromatids break and are
exchanged as homologous chromosomes
separate. As separation occurs, points of
interchange are temporarily united and form
an X-like structure, a chiasma (Fig 2.4C).
Crossover

• As a result of meiotic divisions:

– Genetic variability is enhanced through :
• crossover, which redistributes genetic material
• random distribution of homologous
chromosomes to the daughter cells
– Each germ cell contains a haploid number of
chromosomes, so that at fertilization the diploid
number of 46 is restored.
Meiosis & Crossover
Polar Bodies

• During meiosis, one primary oocytes gives rise

to four daughter cells, each with 22 + X
chromosomes (Fig. 2.5A).
• Only one of these develops into a mature
gametes, however, the oocyte; the other
three, the polar bodies, receive little
cytoplasm and degenerate during subsequent
development.
Polar Bodies

• Similarly, one primary spermatocyte gives rise

to four daughter cells, two with 22 + X
chromosomes and two with 22 + Y
chromosomes (Fig. 2.5B).

• In contrast to oocyte formation, all four

develop into mature gametes.
Polar Bodies
Morphological Changes During Maturation
of the Gametes

Oogenesis

• Oogenesis is the process whereby oogonia

differentiate into mature oocytes
Maturation of Oocytes Begins Before Birth

• Once PGCs have arrived in the gonad of a

genetic female, they differentiate into oogonia
(Fig. 2.1.6. A, B).
• These cells undergo a number of mitotic
divisions, and by the end of the third month,
they arranged in clusters surrounded by a
layer of flat epithelial cells (Fig. 2.17)
Maturation of Oocytes Begins Before Birth
Maturation of Oocytes Begins Before Birth

• Whereas all of the oogonia in one cluster are

probably derived from a single cell, the flat
epithelial cells, known as follicular cells,
originate from surface epithelium covering the
ovary.
• The majority of oogonia continue to divide by
mitosis, but some of them arrest their cell
division in prophase of meiosis I and form
primary oocytes (Figs. 2.16C and 2.17A).
Maturation of Oocytes Begins Before Birth

• During the next few months, oogonia increase

rapidly in number, and by the 5th month of
prenatal development the total number of
germ cells in the ovary reaches its maximum,
estimated at 7 million.
• At this time, cell death begins, and many
oogonia as well as primary oocytes
degenerate and become atretic.
Maturation of Oocytes Begins Before Birth

• By the 7th month, the majority of oogonia have

degenerated except for a few near the surface.
• All surviving primary oocytes have entered
prophase of meiosis I, and most of them are
individually surrounded by a layer of flat follicular
epithelial cells (Fig. 2.17B)
• A primary oocyte, together with its surrounding
flat epithelial cells, is known as a primordial
follicle (Fig. 2.18A).
Maturation of Oocytes Begins Before Birth
Maturation of Oocytes Begins Before Birth
Maturation of Oocytes Continues at Puberty

• Near the time of birth, all primary oocytes have started

prophase of meiosis I, but instead of proceeding into
metaphase, they enter the diplotene stage, a resting
stage during prophase that is characterized by a lacy
network of chromatin (Fig. 2.17 C).
• Primary oocytes remain arrested in prophase and do
not finish their first meiotic division before puberty is
reached.
• This arrested state is produced by oocyte maturation
inhibitor (OMI), a small peptide secreted by follicular
cells.
Maturation of Oocytes Continues at Puberty

• The total number of primary oocytes at birth is

estimated to vary from 600,000 to 800,000.
• During childhood, most oocytes become atretic;
only approximately 40,000 are present by the
beginning of puberty, and fewer than 500 will be
ovulated.

• Some oocytes that reach maturity late in life have

been dormant in the diplotene stage of the first
meiotic division for 40 years or more before
ovulation
Maturation of Oocytes Continues at Puberty

• Whether the diplotene stage is the most

suitable phase to protect the oocyte against
environmental influences is unknown. The fact
that the risk of having children with
chromosomal abnormalities increases with
maternal age indicates that primary oocytes
are vulnerable to damage as they age.
Maturation of Oocytes Continues at Puberty

• At puberty, a pool of growing follicles is

established and continuously maintained from
the supply of primordial follicles.
• Each month, 15 to 20 follicles selected from
this pool begin to mature. Some of these die,
whereas others begin to accumulate fluid in a
space called the antrum, thereby entering the
antral or vesicular stage. (Fig 2.19 A)
Maturation of Oocytes Continues at Puberty

• Fluid continues to accumulate such that,

immediately prior to ovulation, follicles are
quite swollen and are called mature vesicular
follicles or graafian follicles (Fig. 2.19B).
• The antral stage is the longest, whereas the
mature vesicular stage encompasses
approximately 37 hours prior to ovulation.
Maturation of Oocytes Continues at Puberty
Maturation of Oocytes Continues at Puberty

• As primordial follicles begin to grow, surrounding

follicular cells change from flat to cuboidal and
proliferate to produce a stratified epithelium of
granulosa cells, and the unit is called a primary follicle
(Fig. 2.18B,C).
• Granulosa cells rest on a basement membrane
separating them from surrounding ovarian connective
tissue (stromal cells) that form the theca folliculi.
• Also, granulosa cells and the oocyte secrete a layer of
glycoproteins on the surface of the oocyte, forming the
zona pellucida (Fig. 2.18C).
Maturation of Oocytes Continues at Puberty
Maturation of Oocytes Continues at Puberty

• As follicles continue to grow, cells of the theca

folliculi organize into an inner layer of
secretory cells, the theca interna, and an
outer fibrous capsule, the theca externa.
Maturation of Oocytes Continues at Puberty

• Also, small, finger-like processes of the

follicular cells extend across the zona pellucida
and interdigitate with microvilli of the plasma
membrane of the oocyte. These processes are
important for transport of materials from
follicular cells to the oocyte.
Maturation of Oocytes Continues at Puberty

• As development continues, fluid-filled spaces appear

between granulosa cells. Coalescence of these
spaces forms the antrum, and the follicle is termed a
vesicular or an antral follicle. Initially, the antrum is
crescent-shaped, but with time, it enlarges.
Maturation of Oocytes Continues at Puberty

• Granulosa cells surrounding the oocyte remain

intact and form the cumulus oophorus.
• At maturity, the mature vesicular (graafian)
follicle may be 25 mm or more in diameter. It
is surrounded by the theca interna, which is
composed of cells having characteristics of
steroid secretion, rich in blood vessels, and
the theca externa, which gradually merges
with the ovarian connective tissue (Fig 2.19).
Maturation of Oocytes Continues at Puberty
Maturation of Oocytes Continues at Puberty

• With each ovarian cycle, a number of follicles

begin to develop, but usually, only one reaches
full maturity. The others degenerate and become
atretic. When the secondary follicle is mature, a
surge in luteinizing hormone (LH) induces the
preovulatory growth phase.

• Meiosis I is completed, resulting in formation of

two daughter cells of unequal size, each with 23
double-structured chromosomes (Figs. 2.20A,B).
Maturation of Oocytes Continues at Puberty
Maturation of Oocytes Continues at Puberty

• One cell, the secondary oocyte, receives most of

the cytoplasm; the other, the first polar body,
receives practically none.
• The first polar body lies between the zona
pellucida and the cell membrane of the
secondary oocytes in the perivitelline space (Fig.
2.20 B).
• The cell then enters meiosis II but arrests in
metaphase approximately 3 hours before
ovulation.
Maturation of Oocytes Continues at Puberty

• Meiosis II is completed only if the oocyte is

fertilized; otherwise, the cell degenerates
approximately 24 hours after ovulation. The
first polar body may undergo a second division
(Fig. 2.20C)
Spermatogenesis

• Spermatogenesis, which begins at puberty,

includes all of the events by which
spermatogenia are transformed into
spermatozoa.
Maturation of Sperm Begins at Puberty

• At birth, germ cells in the male infant can be

recognized in the sex cords of the testis as
large, pale cells surrounded by supporting
cells (Fig. 2.21A).
• Supporting cells, which are derived from the
surface epithelium of the testis in the same
manner as follicular cells, become
sustentacular cells, or Sertoli cells (Fig. 2.2
IB).
Maturation of Sperm Begins at Puberty
Maturation of Sperm Begins at Puberty

• Shortly before puberty, the sex cords acquire a

lumen and become the seminiferous tubules.
• At about the same time, PGCs give rise to
spermatogonial stem cells. At regular
intervals, cells emerge from this stem cell
population to form type A spermatogonia,
and their production marks the initiation of
spermatogenesis
Maturation of Sperm Begins at Puberty

• Type A cells undergo a limited number of mitotic

divisions to form clones of cells. The last cell division
produces type B spermatogonia, which then divide
to form primary spermatocytes (Figs. 2.21B and
2.22).
• Primary spermatocytes then enter a prolonged
prophase (22 days) followed by rapid completion of
meiosis I and formation of secondary
spermatocytes.
• During the second meiotic division, these cells
immediately begin to form haploid spermatids
(Figs. 2.21B to 2.23).
Maturation of Sperm Begins at Puberty

• Throughout this series of events, from the time

type A cells leave the stem cell population to
formation of spermatids, cytokinesis is
incomplete, so that successive cell generations
are joined by cytoplasmic bridges. Thus, the
progeny of a single type A spermatogonium form
a clone of germ cells that maintain contact
throughout diíferentiation (Fig. 2.22).
• Furthermore, spermatogonia and spermatids
remain embedded in deep recesses of Sertoli
cells throughout their development (Fig. 2.21 B).
Fig 2.22. Type A
spermatogonia, derived
from the spermatogonial
stem cell population,
represent the first cells in
the process of
spermatogenesis. Clones
of cells are established,
and cytoplasmic bridges
join cells in each
succeeding division until
individual sperm are
separated from residual
bodies. In fact, the
number of individual
interconnected cells is
considerably greater than
depicted in this figure.
Maturation of Sperm Begins at Puberty
Maturation of Sperm Begins at Puberty
• Sertoli cells support and protect the germ cells,
participate in their nutrition, and assist in the release
of mature spermatozoa.
• Spermatogenesis is regulated by LH production by
the pituitary gland. LH binds to receptors on Leydig
cells and stimulates testosterone production, which
in turn binds to Sertoli cells to promote
spermatogenesis.
• Follicle-stimulating hormone (FSH) is also
essential because its binding to Sertoli cells
stimulates testicular fluid production and synthesis
of intracellular androgen receptor proteins.
Spermiogenesis

• Spermiogenesis is the series of changes

resulting in the transformation of spermatids
into spermatozoa.
Spermiogenesis

• These changes include

1) formation of the acrosome, which covers half of
the nuclear surface and contains enzymes to
assist in penetration of the egg and its
surrounding layers during fertilization (Fig. 2.24);
2) condensation of the nucleus;
3) formation of neck, middle piece, and tail
4) shedding of most of the cytoplasm as residual
bodies that are phagocytized by Sertoli cells.
Spermiogenesis

• The time required for a spermatogonium to

develop into a mature spermatozoon is
approximately 74 days, and approximately 300
million sperm cells are produced daily.
• When fully formed, spermatozoa enter the lumen
of seminiferous tubules. From there, they are
pushed toward the epididymis by contractile
elements in the wall of the seminiferous tubules
• Although initially only slightly motile,
spermatozoa obtain full motility in the
epididymis.
Spermiogenesis
Genetics Disorders
Primordial Germ Cells (PGCs) and Teratomas

• Teratomas are tumors of disputed origin that often

contain a variety of tissues, such as bone, hair,
muscle, gut epithelia, and others.

• It is thought that these tumors arise from

pluripotent stem cells that can differentiate into
any of the three germ layers or their derivatives.
Some evidence suggests that PGCs that have
strayed from their normal migratory paths could be
responsible (Fig. 2.2). Another source may be
epiblast cells that give rise to all three germ layers
during gastrulation.
Primordial Germ Cells (PGCs) and Teratomas

Figure 2.2. Oropharyngeal

Teratoma. These tumor may
arise from PGCs or epiblast
cells, both of which are
pluripotent. Tissues within the
tumors include derivatives of
all three germ layers and may
include gut, bone, skin, teeth,
and so forth.
Birth Defects and Spontaneous Abortions:
Chromosomal and Genetic Factors

• Chromosomal abnormalities, which may be

numerical or structural, are important causes
of birth defects and spontaneous abortions.
Trisomy 21 (Down Syndrome)

• Down Syndrome is caused by an extra copy of

chromosome 21.
• Clinical Features:
Intellectual disability
Craniofacial abnormalities, including upward
stanting eyes, epicanthal fold (extra skin fold at
the medial corners of the eyes), flat facies, and
small ears
Cardiac defects
Hipotonia
Numerical Abnormalities
Trisomy 21 (Down Syndrome)

Karyotype of trisomy 21
Numerical Abnormalities
Trisomy 21 (Down Syndrome)

Numerical Abnormalities
Trisomy 13

• Clinical Features:
Intellectual disability
Holoprosencephaly
Congenital heart defects
Deafness
Cleft lip and palate
Eye defects, such as
microphtalmia,
anopthalmia, and
coloboma
Bilateral cleft lip, the slopping
forehead, and anophthalmia

Numerical Abnormalities
Klinefelter Syndrome (47 XXY)

• Clinical features of this syndrome that found

only in males usually detected by
amniocentesis, are sterility, testicular atrophy,
hyalinization of the seminiferous tubules, and
usually gynecomastia.

Numerical Abnormalities
Turner Syndrome (45X)

• Turner Syndrome is the only monosomy

compatible with life, 98% of all fetuses with
syndrome are spontaneously aborted.
• The few that survive are unmistakably female in
appearance and are characterized by the absence
of ovaries [gonadal dysgenesis] and short
stature.
• Other clinical features are webbed neck,
lymphedema of the extremities, skeletal
deformities, and a broad chest with widely
spaced nipples.

Numerical Abnormalities
Turner Syndrome (45X)

Numerical Abnormalities
Cri-du-chat syndrome

• A well known syndrome, caused by partial

deletion of the short arm of chromosome 5.
• Affected infants have a cat-like cry,
microcephaly, intellectual disability, and
congenital heart disease.

Structural Abnormalities
Angelman syndrome

• This syndrome cause by

microdeletion that occurs
on the maternal
chromosome.
• Clinical features of this
syndrome are intellectual
disability, cannot speak,
exhibit poor motor
development and are
prone to unprovoked and
prolonged periods of
laughter
Structural Abnormalities
Prader-Willi syndrome

• This syndrome cause by

microdeletion that
occurs on the paternal
chromosome 15.
• Affected individuals are
characterized by
hypotonia, obesity,
intellectual disability,
hypogonadism, and
undescended testis.

Structural Abnormalities
Thank You