GAMETOGENESIS
GAMETOGENESIS
CAROLINE
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LEARNING OBJECTIVES/AIMS
• Understand meiosis
• Understand spermatogenesis
• Understand oogenesis
• Application of this knowledge
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definition
• Involve the long series of changes that male
and female sex cells undergoes.
• convert them genetically and phenotypically
into mature gametes,which are capable of
participating in the process of fertilization.
4 Phases of gametogenesis
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PROPHASE
• Five sections:
• Leptotene
• Zygotene
• Pachytene
• Diplotene
• Diakinesis
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SOME QUESTIONS WE NEED TO ANSWER
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© 2005 Elsevier
MEIOSIS
• A special type of cell division that involves two
meiotic cell divisions occurring in germ cells
only
• Diploid germ cells give rise to haploid gametes
• The first meiotic division is a reduction
division because the chromosome number is
reduced from diploid to haploid by pairing of
homologous chromosomes in prophase and
their segregation at anaphase.
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• Homologous chromosomes (one from each
parent) pair during prophase and separate
during anaphase, with one representative of
each pair randomly going to each pole of the
meiotic spindle.
• The spindle connects to the chromosome at
the centromere.
• At this stage, they are double-chromatid
chromosomes.
• The X and Y chromosomes are not homologs,
but they have homologous segments at the
tips of their short arms.
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• They pair in these regions only.
• By the end of the first meiotic division, each
new cell formed (secondary spermatocyte or
secondary oocyte) has the haploid
chromosome number (double-chromatid
chromosomes).
• The separation or disjunction of paired
homologous chromosomes is the physical
basis of segregation, the separation of allelic
genes during meiosis.
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Figure 2-2 Diagrammatic representation of meiosis. Two chromosome pairs are shown. A
to D, Stages of prophase of the first meiotic division. The homologous chromosomes
approach each other and pair; each member of the pair consists of two chromatids.
Observe the single crossover in one pair of chromosomes, resulting in the interchange of
chromatid segments. E, Metaphase. The two members of each pair become oriented on
the meiotic spindle. F, Anaphase. G, Telophase. The chromosomes migrate to opposite
poles. H, Distribution of parental chromosome pairs at the end of the first meiotic division.
I to K, Second meiotic division. It is similar to mitosis except that the cells are haploid. 16
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MEIOSIS-II
• The second meiotic division follows the first division
without a normal interphase (i.e., without an intervening
step of DNA replication).
• Each chromosome divides and each half, or chromatid, is
drawn to a different pole; thus, the haploid number of
chromosomes (23) is retained and each daughter cell
formed by meiosis has the reduced haploid number of
chromosomes, with one representative of each
chromosome pair (now a single-chromatid chromosome).
• The second meiotic division is similar to an ordinary
mitosis except that the chromosome number of the cell
entering the second meiotic division is haploid.
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OUTCOME OF MEIOSIS
• Provides constancy of the chromosome number from
generation to generation by reducing the
chromosome number from diploid to haploid,
thereby producing haploid gametes.
• Allows random assortment of maternal and paternal
chromosomes between the gametes.
• Relocates segments of maternal and paternal
chromosomes by crossing over of chromosome
segments, which "shuffles" the genes and produces a
recombination of genetic material.
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SPERMATOGENESIS
• Spermatogenesis is the sequence of events by
which spermatogonia are transformed into
mature sperms.
• This maturation process begins at puberty.
• Spermatogonia, which have been dormant in the
seminiferous tubules of the testes since the fetal
period, begin to increase in number at puberty.
• After several mitotic divisions, the
spermatogonia grow and undergo changes.
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• Mature sperms are free-swimming, actively
motile cells consisting of a head and a tail.
• The neck of the sperm is the junction between
the head and tail.
• The head of the sperm forms most of the bulk of
the sperm and contains the haploid nucleus.
• The anterior two thirds of the nucleus is covered
by the acrosome, a caplike saccular organelle
containing several enzymes.
• When released, these enzymes facilitate
dispersion of the follicular cells of the corona
radiata and sperm penetration of the zona
pellucida during fertilization.
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• The tail of the sperm consists of three
segments: middle piece, principal piece,
and end piece.
• The tail provides the motility of the
sperm that assists its transport to the site
of fertilization.
• The middle piece of the tail contains
mitochondria, which provide the
adenosine triphosphate necessary for
activity.
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9 Mitochondrion
1 Plasma membrane 10 Axoneme
2 Outer acrosomal membrane 11 Anulus
3 Acrosome 12 Ring fibers
4 Inner acrosomal membrane A Head
5 Nucleus B Neck
6 Proximal centriole C Mid piece
7 Rest of the distal centriole D Principal piece
8 Thick outer longitudinal fibers E Endpiece
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CONTROL OF SPERMATOGENESIS
• Many genes and molecular factors are
implicated in spermatogenesis.
• E.g. proteins of the Bcl-2 family are involved in
the maturation of germ cells, as well as their
survival at different stages.
• For normal spermatogenesis, the Y
chromosome is essential; microdeletions
result in defective spermatogenesis and
infertility.
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THE TEMPORAL COURSE OF SPERMATOGENESIS
• The approximate 64 day cycle of the spermatogenesis can be
subdivided into four phases that last differing lengths of time:
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• primordial germ cells give rise to spermatogonial stem cells.
• cells emerge from this stem cell population to form type A
spermatogonia, and their production marks the initiation
of spermatogenesis.
• Type A cells undergo a limited number of mitotic divisions
to form a clone of cells.
• The last cell division produces type B spermatogonia,
which then divide to form primary spermatocytes.
• 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 29
NB
• Furthermore, spermatogonia and spermatids remain embedded
in deep recesses of Sertoli cells throughout their development.
• Sertoli cells fnxs; support and protect the germ cells, participate
in their nutrition, and assist in the release of mature
spermatozoa.
• Spermatogenesis is regulated by luteinizing hormone (LH)
production by the pituitary.
• 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.
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human spermatogenesis
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Spermiogenesis
• Refers to series of changes resulting in the transformation of spermatids
into spermatozoa
• These changes include;
• (a) 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.
• (b) condensation of the nucleus;
• (c) formation of neck, middle piece, and tail;
• (d) shedding of most of the cytoplasm.
• In humans, the time required for a spermatogonium to develop into a
mature spermatozoon is approximately 64 days.
• When fully formed, spermatozoa enter the lumen of seminiferous
tubules, pushed toward the epididymis by contractile elements in the
wall of the seminiferous tubules.
• Although initially only slightly motile,spermatozoa obtain full motility in
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the epididymis.
spermiogenesis
OOGENESIS
• Oogenesis (ovogenesis) is the sequence of events by
which oogonia are transformed into mature
oocytes.
• begins before birth and is completed after puberty.
• continues to menopause( permanent cessation of
the menses).
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PRENATAL MATURATION OF OOCYTES
• During early fetal life, oogonia proliferate by mitosis.
• Oogonia enlarge to form primary oocytes before birth.
• As a primary oocyte forms, connective tissue cells
surround it and form a single layer of flattened, follicular
epithelial cells.
• As the primary oocyte enlarges during puberty, the
follicular epithelial cells become cuboidal in shape and
then columnar, forming a primary follicle.
• The primary oocyte soon becomes surrounded by a
covering of amorphous acellular glycoprotein material, the
zona pellucida.
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1 Cytoplasma of the oocyte (ooplasma)
2 Cell nucleus
3 Nucleolus
4 Pellucid zone
5 Corona radiata cells
6 Cytoplasmic processes of a corona radiata cell
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• Scanning electron microscopy of the surface of
the zona pellucida reveals a regular meshlike
appearance with intricate fenestrations.
• Primary oocytes begin the first meiotic
division before birth, but completion of
prophase does not occur until adolescence.
• The follicular cells surrounding the primary
oocyte are believed to secrete a substance,
oocyte maturation inhibitor, which keeps the
meiotic process of the oocyte arrested.
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oogenesis
Meiotic output
Four functioning, small (head 4 mm), motile One large, immotile oocyte (diameter 120
spermatozoids at the end of the meiosis mm) and three shriveled polar bodies are
left at the end of the meiosis
Fetal period
No meiotic divisions Entering into meiosis (arrested in the
dictyotene stage)
No germ cell production Production of the entire supply of germ cells
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• 23 chromosomes in the complement,
consisting of 22 autosomes and one
sex chromosome .
• The difference in the sex
chromosome complement of sperms
forms the basis of primary sex
determination.
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VIABILITY OF GAMETES
• Studies on early stages of development indicate that
human oocytes are usually fertilized within 12 hours
after ovulation.
• In vitro observations have shown that the oocyte
cannot be fertilized after 24 hours and that it
degenerates shortly thereafter.
• Most human sperms probably do not survive for more
than 48 hours in the female genital tract.
• Some sperms are stored in folds of the mucosa of the
cervix and are gradually released into the cervical canal
and pass through the uterus into the uterine tubes.
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• The short-term storage of sperms in
the cervix provides a gradual release
of sperms and thereby increases the
chances of fertilization.
• Sperms and oocytes can be stored
frozen for many years to be used in
assisted reproduction.
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TRANSPORTATION OF GAMETES
• Oocyte Transport
• The secondary oocyte is expelled at ovulation
from the ovarian follicle with the escaping
follicular fluid.
• During ovulation, the fimbriated end of the
uterine tube becomes closely applied to the
ovary.
• The fingerlike processes of the tube, fimbriae,
move back and forth over the ovary.
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• The sweeping action of the fimbriae and fluid
currents produced by the cilia of the mucosal
cells of the fimbriae "sweep" the secondary
oocyte into the funnel-shaped infundibulum
of the uterine tube.
• The oocyte passes into the ampulla of the
tube, mainly as the result of peristalsis-
movements of the wall of the tube
characterized by alternate contraction and
relaxation-that pass toward the uterus.
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SPERM TRANSPORT
• From their storage site in the epididymis, mainly in its
tail, the sperms are rapidly transported to the urethra by
peristaltic contractions of the thick muscular coat of the
ductus deferens .
• The accessory sex glands-seminal glands (vesicles),
prostate, and bulbourethral glands-produce secretions
that are added to the sperm-containing fluid in the
ductus deferens and urethra.
• From 200 to 600 million sperms are deposited around
the external os of the uterus and in the fornix of the
vagina during sexual intercourse. The sperms pass slowly
through the cervical canal by movements of their tails.
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• The enzyme vesiculase, produced by
the seminal glands, coagulates some
of the semen or ejaculate and forms
a vaginal plug that may prevent the
backflow of semen into the vagina.
• When ovulation occurs, the cervical
mucus increases in amount and
becomes less viscid, making it more
favorable for sperm transport.
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• The reflex ejaculation of semen may be divided
into two phases:
• Emission: Semen is delivered to the prostatic
part of the urethra through the ejaculatory
ducts after peristalsis of the ductus deferens;
emission is a sympathetic response.
• Ejaculation: Semen is expelled from the urethra
through the external urethral orifice; this
results from closure of the vesical sphincter at
the neck of the bladder, contraction of urethral
muscle, and contraction of the
bulbospongiosus muscles.
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• Passage of sperms through the uterus and
uterine tubes results mainly from muscular
contractions of the walls of these organs.
• Prostaglandins in the semen are thought to
stimulate uterine motility at the time of
intercourse and assist in the movement of
sperms to the site of fertilization in the
ampulla of the tube.
• Fructose, secreted by the seminal glands, is an
energy source for the sperms in the semen.
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• The volume of sperm or ejaculate (sperms
suspended in secretions from accessory sex
glands) averages 3.5 mL, with a range of 2 to 6
mL.
• The sperms move 2 to 3 mm per minute, but
the speed varies with the pH of the
environment.
• They are nonmotile during storage in the
epididymis, but become motile in the ejaculate.
• They move slowly in the acid environment of
the vagina, but move more rapidly in the
alkaline environment of the uterus.
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• It is not known how long it takes sperms to
reach the fertilization site, but the time of
transport is probably short.
• Motile sperms have been recovered from the
ampulla of the uterine tube 5 minutes after
their deposition near the external uterine os.
• Some sperms, however, take as long as 45
minutes to complete the journey.
• Only approximately 200 sperms reach the
fertilization site. Most sperms degenerate and
are resorbed by the female genital tract.
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MATURATION OF SPERMS
• Freshly ejaculated sperms are unable to fertilize oocytes.
• Sperms must undergo a period of conditioning-
capacitation-lasting approximately 7 hours.
• During this period, a glycoprotein coat and seminal
proteins are removed from the surface of the sperm's
acrosome.
• The membrane components of the sperms are
extensively altered.
• Capacitated sperms show no morphologic changes, but
they are more active.
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• Sperms are usually capacitated in the uterus
or uterine tubes by substances secreted by
these parts of the female genital tract.
• During in vitro fertilization, a process whereby
several oocytes are placed in an artificial
medium to which sperms are added for
fertilization, capacitation is induced by
incubating the sperms in a defined medium
for several hours. Completion of capacitation
permits the acrosome reaction to occur.
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Acrosome reaction
• The intact acrosome of the sperm binds to a
glycoprotein (ZP3) on the zona pellucida.
• Sperm plasma membrane, calcium ions,
prostaglandins, and progesterone play a critical role
in the acrosome reaction.
• The acrosome reaction of sperms must be
completed before the sperm can fuse with the
oocyte.
• When capacitated sperms contact corona radiata,
they undergo complex molecular changes- leading to
development of perforations in the acrosome.
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• Multiple point fusions of the plasma
membrane of the sperm and the external
acrosomal membrane occur.
• Breakdown of the membranes at these
sites produces apertures.
• The changes induced by the acrosome
reaction are associated with the release
of enzymes, including hyaluronidase and
acrosin, from the acrosome that facilitate
fertilization.
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PATHOLOGY OF GAMETOGENESIS
• Abnormal Gametogenesis
• Disturbances of meiosis during
gametogenesis, e.g., nondisjunction, result in
the formation of chromosomally abnormal
gametes.
• If involved in fertilization, these gametes with
numerical chromosome abnormalities cause
abnormal development such as occurs in
infants with Down syndrome.
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ABNORMAL GAMETES
• The ideal maternal age for reproduction is generally
considered to be from 18 to 35 years.
• The likelihood of chromosomal abnormalities in the
embryo increases after the mother is 35.
• In older mothers, there is an appreciable risk of Down
syndrome or some other form of trisomy in the infant.
• The likelihood of a fresh gene mutation (change in DNA)
also increases with age. The older the parents are at the
time of conception, the more likely they are to have
accumulated mutations that the embryo might inherit.
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• For fathers of children with fresh mutations, such as
the one causing achondroplasia, this age relationship
has continually been demonstrated.
• During gametogenesis, homologous chromosomes
sometimes fail to separate- nondisjunction-some
gametes have 24 chromosomes and others only 22.
• If a gamete with 24 chromosomes unites with a
normal one with 23 chromosomes during
fertilization, a zygote with 47 chromosomes forms -
trisomy because of the presence of three
representatives of a particular chromosome instead
of the usual two.
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• If a gamete with only 22
chromosomes unites with a normal
one, a zygote with 45 chromosomes
forms- monosomy because only one
representative of the particular
chromosome pair is present.
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ABNORMAL SPERMS
• As many as 10% of sperms in an ejaculate are grossly
abnormal (e.g., with two heads)
• Most morphologically abnormal sperms are unable to
pass through the mucus in the cervical canal.
Measurement of forward progression is a subjective
assessment of the quality of sperm movement.
• Radiography, severe allergic reactions, and certain
antispermatogenic agents have been reported to
increase the percentage of abnormally shaped sperms.
Such sperms are not believed to affect fertility unless
their number exceeds 20%.
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ABNORMAL OVA
• Although some oocytes have two or three nuclei,
these cells die before they reach maturity.
• Similarly, some ovarian follicles contain two or
more oocytes, but this phenomenon is
infrequent.
• Although compound follicles could result in
multiple births, it is believed that most of them
never mature and expel the oocytes at ovulation.
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SPERM COUNTS
• During evaluation of male fertility, an analysis of semen is
made. Sperms account for less than 10% of the semen.
• The remainder of the ejaculate consists of the secretions
of the seminal glands, prostate, and bulbourethral glands.
There are usually more than 100 million sperms per
milliliter of semen in the ejaculate of normal males.
• Although there is much variation in individual cases, men
whose semen contains 20 million sperms per milliliter, or
50 million in the total specimen, are probably fertile.
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• A man with fewer than 10 million sperms per
milliliter of semen is likely to be sterile, especially
when the specimen contains immotile and abnormal
sperms.
• For potential fertility, 50% of sperms should be
motile after 2 hours and some should be motile after
24 hours.
• Male infertility may result from a low sperm count,
poor sperm motility, medications and drugs,
endocrine disorders, exposure to environmental
pollutants, cigarette smoking, abnormal sperms, or
obstruction of a genital duct such as in the ductus
deferens and represents approximately 30% to 50%
of infertility in couples.
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VASECTOMY
• The most effective method of permanent
contraception in the male is vasectomy, or
excision of a segment of each ductus (vas)
deferens.
• This surgical procedure is reversible in more
than 50% of cases.
• Following vasectomy, there are no sperms in
the semen or ejaculate, but the volume is the
same.
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Dispermy and Triploidy
• Although several sperms begin to penetrate the
corona radiata and zona pellucida, usually only one
sperm penetrates the oocyte and fertilizes it.
• Two sperms may participate in fertilization during an
abnormal process known as dispermy, resulting in a
zygote with an extra set of chromosomes.
• Triploid conceptions account for approximately 20%
of chromosomally abnormal spontaneous abortions.
Triploid embryos (69 chromosomes) may appear
normal, but they nearly always abort.
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• Aborted triploid fetuses have severe
intrauterine growth retardation,
disproportionately small trunks, and
anomalies in the central nervous
system.
• A few triploid infants have been
born, but they all died shortly after
birth.
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THANK YOU
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