GAMETOGENESIS
• DEFINITION: Human gametogenesis is the process by
which diploid germ cells (Spermatogonia or Oogonia)
form haploid cells (Spermatozoa or Ova) through
sequences of cell divisions and cell differentiation. It
can simply be described as a procedure by which
sperms and ova are designed in the testes and ovaries
respectively.
• In the male, the process is known as Spermatogenesis
and produces spermatozoa, while in the female it is
refer to as Oogenesis and results in the formation of
ova (Eggs)
SPERMATOGENESIS
• Spermatogenesis is the process by which spermatogonia
are transformed into mature spermatozoa
• Spermatogenesis takes place in the seminiferous
tubules. The germinal tubules are lined with germinal
epithelium which largely comprises of primordial germ
cells and supporting cells (Sertoli cells)
• Males start producing sperms when they attain puberty.
Sperms are produced in large quantity (100 to 200 million
per day) to maximise the possibility of sperm reaching
the liberated egg
• Sperms are produced continually, because males need to
utilize the small fertility window of the female
Spermatogenesis continue
• Spermatogenesis has three sequential phases:
1. Mitotic proliferation phase
2. Meiotic division phase
3. Cytodifferentiation phase
• Mitotic proliferation phase: is a phase that produces
large number of cells through mitotic divisions.
• Just before puberty, the sex cords of the testes acquire
lumen and becomes seminiferous tubules and
concurrently, primordial germ cells give rise to
spermatogonial stem cells (SSCs) which form a pool
Diagram showing spermatogenesis (Adapted from
online biology)
Mitotic proliferation phase continue
• At successive interval, the SSC pool releases some cells to form
Spermatogonia Type A and their production marks the
beginning of spermatogenesis
• Each of these type A spermatogonia undergoes a number of
mitotic divisions to produce a clone of 16 cells
• Each of the cells in the clone undergoes a further several mitotic
divisions to form type B spermatogonia
• The number of mitotic divisions from SSC to type B
spermatogonia determines the total number of cells in the clone.
Their number is however reduced by apoptosis to a large extent
• Each of these Type B spermatogonia then undergoes further
mitotic divisions to form Resting Primary spermatocyte which
marks the end of proliferation phase
Mitotic proliferation phase continue
• It is to be noted that all through the mitotic phase of
spermatogenesis, nuclear division (Karyokinesis) is complete,
but cytoplasmic division (Cytokinesis) is incomplete. Hence the
primary spermatocyte derived from one type A
spermatogonium are linked together by thin cytoplasmic
bridges
• This linkage persist even in the meiosis phase and continue till
the formation of mature spermatozoa
Meiotic division phase
• The meiotic division phase is aimed at reducing the chromosome
number to half and to create genetic diversity
• Prior to entering the prophase 1 of first meiosis, each resting primary
spermatocyte duplicates its DNA content
• These primary spermatocytes with the duplicated DNA then enter
the prophase 1 of first meiosis which is very prolonged and lasted for
about 22 days as it passes through its different stages (leptotene,
zygotene, pachytene, diplotene and diakinesis)
• During the pachytene stage of prophase 1, the sister chromatid
strands on the paired homologous chromosomes come together to
form synaptonemal contacts during which the chromatids break,
exchanged segments of genetic materials and then rejoin, thereby
shuffling the genetic information before separating themselves
Meiotic division phase continue
• The first meiotic division ends with the separation of
homologous chromosomes to the opposite pole of the
cell on the meiotic spindle, followed by cytokinesis which
results in the formation of two secondary spermatocytes
• The secondary spermatocytes contain a single set of
chromosomes consisting of two chromatids joined at the
centromere.
• The secondary spermatocytes are short-lived as they
quickly enter into the second meiosis during, which the
chromatids separate and move to opposite pole of the
second meiotic spindle
• This is followed by formation of nuclear membrane and
cytokinesis yielding haploid round spermatids
CYTODIFFERENTIATION PHASE
• The Cytodifferentiation phase involves the remodelling or transformation
of the round spermatids into mature spermatozoa and is refer to as
spermiogenesis
• During this process, some major cytoplasmic changes occur. Such
changes include the followings:
I. The spermatids change shape from round to elongated
II. Tail for forward propulsion is formed
III. Mid-piece containing mitochondria is formed. The mitochondria
generate energy for the cell.
IV. Condensation of the nucleus takes place
V. Formation of Acrosome that occupy about half of the head of the sperm
from the Golgi apparatus. The acrosome contains enzyme that aid
penetration of the ova and its surrounding layers during fertilization
VI. Shedding of most of the cytoplasm
Cytodifferentiation phase continue
• The end result of spermiogenesis is the formation of
mature spermatozoa
• With appearance of the spermatozoa, the thin
cytoplasmic bridges rupture and the sperm cells are
released into the lumen of the tubules in a process
called spermiation and are washed along the tubules
with the testicular fluid secreted by the Sertoli cells
• From the seminiferous tubules, the spermatozoa enter
the epididymis during which they become fully motile
Diagram showing the structure of sperm
(Adapted from Boundless biology)
Spermatogenic cycle
• There are about 30 seminiferous tubules per testis in
human. In each of them certain number of spermatogonia
emerge from the SSC pool to commence spermatogenesis
• Once spermatogenesis commences in a tubule from SSC
pool, new spermatogonia cannot emerge to generate a new
clone until several days elapsed
• The period of occurrence of successive spermatogenesis is
said to be constant and species specific. It is 16 days for
human and 12 days for rat
• This cyclical initiation of spermatogenesis is what is refer to
as spermatogenic cycle
OOGENESIS
• Oogenesis is the process of transformation of oogonia to a mature
ova.
• It begins during foetal life. When the primordial germ cells arrived in
the ovary, they are differentiated into Oogonia which undergo mitotic
divisions and are arranged in clusters surrounded by follicular cells
• Similar to spermatogenesis, Oogenesis also passes through three
processes – Mitotic proliferation, meiosis division for genetic
reshuffling and chromosomal reduction and cytodifferentiation
• Unlike in the male, mitotic proliferation in the female is slight, hence
only limited number of oogonia are produced as only one or few
oocytes are released during each cycle
• The oogonia then undergo several mitotic divisions and by 20
weeks of development yielded the maximum estimated number of 7
million
Diagram showing Oogenesis process (Adapted
from online biology)
Oogenesis continue
• However, due to apoptosis, the number of oogonia is reduced to 2 million.
At birth the total number of oogonia left in the ovary is between 700,000 to
2 million
• By beginning of puberty only 400,000 oogonia remain in the ovary as
greater number of them became atretic during childhood
• Of the 400,000, only about 400 – 500 will be ovulated
• Most of the oogonia continue to divide by mitosis, but few went into
prophase I of first meiosis and arrest at the diplotene stage to form
primary oocytes
• Just before birth, all the primary oocytes have entered into meiosis I, with
most arrested at diplotene instead of proceeding to metaphase. Also,
most of them are individually surrounded by flat epithelial cells (follicular
cells) to form primordial follicle
• The primary oocyte remain in prophase and do not complete their first
meiosis before puberty
Meiosis division phase of oogenesis
• At puberty pool of growing follicle is established and replenished regularly
from the primordial follicles
• Every month, about 15 to 20 follicles are selected from the pool to
undergo maturation as they pass through different stages – primary or
preantral, secondary or antral (Graafian) and preovulatory or tertiary
follicle
• The preantral stage is the longest while the preovulatory stage is the
shortest and last for 37 hours before ovulation
• The growth from primordial follicle to preantral follicle is characterised by
initial increase in its diameter from 20 µm to between 200µm and 400µm.
• During this period, the oocyte within also increases in size to its final
diameter of 60 - 120µm as the surrounding follicular cells change from
flat to cuboidal and proliferate to form a stratified epithelium of granulosa
cells. The whole unit is now known as primary follicle
Meiosis division phase of oogenesis
• The granulosa cells that surround the primary oocyte lie
on a basement membrane that separate the oocyte from
the surrounding stromal cells known as theca folliculi
• As the follicle continue to grow, the granulosa cells and
the oocyte secrete glycoprotein know as zona pellucida
that envelops the oocyte. Also, the theca folliculi is
differentiated into inner layer of secretory cells known as
theca interna and an outer fibrous layer known as theca
externa
• The development of these two thecal layers marks the
end of the preantral follicular stage
Transition from preantral to antral follicle
• As the follicle continues to grow, the granulosa cells also proliferate resulting in
further increase in size
• In between the granulosa cells, a viscous fluid begins to appear and later these
drops of fluids coalesce to form a single follicular fluid space called Antrum
and this marks the beginning of the antral or secondary follicular phase of
development
• The follicular antrum then divides the granulosa cells into an inner group that
surround the oocyte known as Cumulus oophorus and a peripheral group known
as Mural granulosa cells
• Increase in follicular size now depends on an increase in size of the follicular
antrum and at maturity its size is about 25mm or more in diameter
• The fully matured antral follicle is now ready to enter the preovulatory phase
whose commencement is induced by the LH surge. It last for only about 37
hours before being ovulated. This marks the end of meiosis I, leading to the
formation of two unequal daughter cells – the secondary oocyte that receives
most of the cytoplasm and the first polar body with virtually none
Diagram showing Antral follicle (Adapted from online
biology)
Oogenesis continue
• The secondary oocyte then enters meiosis 11 and get
arrested in metaphase stage about 3 hours before
ovulation
• Meiosis two is completed only if fertilization occurs. If
the oocyte is not fertilized, it degenerates about 24
hours after ovulation
CLINICAL IMPLICATION
• During spermatogenesis, a number of abnormal spermatozoa
are frequently observed.
• They include abnormalities of the head:
1. Globozoospermia – most of the sperm cells have small round
heads, without acrosome. Such men are usually infertile
2. Double head – one mid-piece and tail, but with two heads
3. Tapered head – head is cylindrical and tapers at the apex
4. Amorphous heads – the head is without a specific shape
5. Pyriform head – head appears triangular in shape with the
apex wide and a narrow region attached to the mid-piece
6. Vacuolated head – head has many vacuoles
Abnormalities in spermatogenesis
• Neck and midpiece defects:
1. Bent neck
2. Asymmetrical insertion of the neck/ midpiece
3. Thick and thin insertion
• Tail defects:
1. Coiled tail
2. Short tail and
3. Bent tail
• Excess residual cytoplasm
Pictorial representation of sperm defects (
Adapted from WHO laboratory manual)
Abnormalities of oogenesis
• Compared to spermatogenesis, in the human fewer
abnormalities are observed during Oogenesis.
• Occasionally, one ovarian follicle may contain two or
three oocytes. Such follicles usually degenerate before
reaching maturity. In rare cases, twins or triplets could
result from such follicles
• There are also some situations where one primary
oocyte may contain two or three nuclei (Binucleated or
trinucleated oocytes). They however, die off before
amturity