GAMETOGENESIS:

Conversion of Germ Cells

into Male and Female
gametes

Jovie E. Nicolas, LPT

Chromosomal Abnormalities

Chromosomal abnormalities that may lead to birth

defects or spontaneous abortion

May be numerical, structural, and genetic

Numerical Abnormalities

• Euploid – exact multiple of n (haploid, diploid)

• Aneuploid – Any chromosome number that is not euploid;
missing chromosome or extra chromosome (ex. Trisomy,
monosomy)
• Nondisjunction – Non-separation of chromosomes.
• Mosaicism – Product of Nondisjunction in mitosis. Some cells
have abnormal chromosome number, some have normal.
• Translocation – chromosomes break and pieces of one
chromosome attach to another
Nondisjunction
Chromosomal Abnormalities

Chromosomal abnormalities that may

lead to birth defects or spontaneous
abortion

Translocation
• chromosomes break and pieces of
one chromosome attach to another

• Translocations are particularly

common between chromosomes 13,
14, 15, 21 and 22 because they
cluster during meiosis
Trisomy 21, Down Syndrome
• extra copy of chromosome 21

• approximately one in 2,000 conceptuses for women under age

35 and one in 100 at age 40

• Features include growth retardation, varying degrees of

intellectual disability, craniofacial abnormalities, cardiac defects

• 95% of cases caused by trisomy 21 (meiotic disjunction); 75% of

these instances, nondisjunction occurs during oocyte formation

• Approximately 4% of cases of Down syndrome, there is an

unbalanced translocation between chromosome 21 and
chromosome 13, 14, 15 or 21

• Final 1% is caused by mosaicism resulting from mitotic

nondisjunction
Trisomy 18, Edward Syndrome
• extra copy of chromosome 18

• Features are intellectual disability, congenital heart

defects, low-set ears and flexion of fingers and
hands, also show micrognathia, renal anomalies,
syndactyly and malformations of the skeletal system

• Incidence is approximately one in 5,000 newborns

• 85% are lost between 10 weeks of gestation and

term

• Those born alive usually die by 2 months of age

• Approximately 5% live beyond 1 year

Trisomy 13, Patau Syndrome
• extra copy of chromosome number 13

• Features are intellectual disability,

holoprosencephaly (single lobe brain), congenital
heart defects, deafness, cleft lip and palate, and
eye defects like microphthalmia, anophthalmia and
coloboma

• Incidence is approximately one in 20,000 live births

• More than 90% of the infants die in the first month

after birth

• Approximately 5% live beyond 1 year

Klinefelter Syndrome (47, XXY)

• boys are born with extra X chromosome with sex

chromatin (Barr) body found in 80% of cases

• Features include sterility, testicular atrophy, hyalinization

of the seminiferous tubules and gynecomastia

• Incidence is approximately one in 500 males

• Nondisjunction of the XX homologous is the most

common causative event

• Sometimes, patients have 48 chromosomes (48, XXXY),

the more X chromosomes, the more likely there will be
some degree of cognitive impairment
Turner Syndrome

• one of the X chromosome is missing or partially missing

• Only monosomy compatible with life but 98% of all

fetuses with the syndrome are spontaneously aborted,
the few that survive are mistakeably female in
appearance

• Features include gonadal dysgenesis and short stature,

webbed neck, lymphedema of the extremities, skeletal
deformities and broad chest with widely spaced nipples

• Approximately 55% are monosomic for X and chromatin

body negative because of nondisjunction; 80% of these
nondisjunction in the male gamete is the cause;
remainder structural abnormalities of X chromosome or
mitotic nondisjunction resulting in mosaicism are the
causes
Triple X Syndrome

• Triple X Syndrome, Trisomy X (47, XXX) = girls

with extra X chromosome

• Often undiagnosed because of their mild

physical features

• Features include taller than average height,

problems with speech and self-esteem, some
have greater intelligence, others may have
intellectual disabilities and behavioral
problems
Structural Abnormalities
• Usually result from chromosomal breakage cause by
environmental factors
• The result of breakage may lead to partial deletion of a
chromosome

• Microdeletions – spanning only a few contiguous genes

(Microdeletion syndrome or Contiguous gene syndrome)
• Fragile sites = are regions of chromosomes that
demonstrate a propensity to separate or break under
certain cell manipulations
Cri-du-chat Syndrome

• partial deletion of the short arm

of chromosome 5

• Infants with cat-like cry,

microcephaly, intellectual
disability and congenital heart
disease
Angelman’s Syndrome

• Microdeletion occurs on the long

arm of chromosome 15

• Microdeletion occurs on maternal

chromosome

• Features include intellectual

disability, cannot speak, exhibit poor
motor development and are prone
to unprovoked and prolonged
periods of laughter
Prader-Willi Syndrome

• Microdeletion occurs on the long

arm of chromosome 15

• Microdeletion occurs on paternal

chromosome

• Features include hypotonia,

obesity, intellectual disability,
hypogonadism and undescended
testes
Miller-Dieker Syndrome

• a contiguous gene syndrome that

may be inherited from either
parent; deletion at 17p13

• Features are lissencephaly

(smooth brain), developmental
delay, seizures and cardiac and
facial abnormalities
DiGeorge Syndrome

• deletion in 22q11

• Features are palatal defects,

conotruncal heart defects (affects
blood flow), speech delay,
learning disorders and
schizophrenia-like disorder
Fragile X Syndrome

• CGG repeats = fragile sites consist of this, only

those in the FMR1 gene on the long arm of the X
chromosome (Xq27) have been correlated with an
altered phenotype that is called the Fragile X
Syndrome

• Features are intellectual disability, large ears,

prominent jaw and large testes

• One per 5,000 individuals is affected

• Males are affected almost exclusively

• Second to Trisomy 21 as a cause of intellectual

disability due to genetic abnormalities
Gene Mutations

• Some congenital malformations are directly attributable to a change in the structure or function of
a single gene called Single Gene Mutation

• Estimated to account for approximately 8% of all human malformations

• Dominant mutation = if a mutant gene produces an abnormality in a single dose, despite the
presence of a normal allele

• Recessive mutation = if both alleles must be abnormal (double dose) or if the mutation is X-linked
in male

• Mutations in many of these same genes are responsible for some congenital abnormalities

• Mutations may also result to inborn errors of metabolism like phenylketonuria, homocystinuria
and galactosemia
Morphological Changes During Maturation of Gametes

Oogenesis
Maturation of the oogonia
into matured oocytes (ovum)
Maturation of Oocytes begins
before Birth
Gonads
Mitosis Mitosis
Some Oogonia develops
into Primary Oocytes,
which arrests during
prophase I of meiosis I
4th month
of the
Embryo
At the end of the 3rd
month, Oogonia and
primary oocytes
arrested in prophase 1
are clustered; covered
by a layer of follicular
cells, which are flat
epithelial cells.
All oogonia and oocytes
in one cluster may have
come from a single PGC
Maturation of Oocytes begins
before Birth
PRIMORDIAL In the diplotene,
FOLLICLE = homologous
chromosomes are
Surviving
attached at chiasmata.
Oocyte +
At the 5th month, surrounding
the number of Primary oocytes remain
follicular cells arrested in prophase
Oogonia and and do not finish their
Oocytes peaks first meiotic division
(approx. 7 before puberty is
million). This is reached. This arrested
followed by a state is produced by
series of apoptosis oocyte maturation
inhibitor (OMI), a small
of majority of
peptide secreted by
Oogonia and Near the time of birth, nofollicular cells
oocytes At the 7th month, only a Oogonium is present,
few oocytes in prophase 600,000 to 800,000
I survives, and they are oocytes are arrested in
individually covered by the diplotene stage of
follicular cells. Prophase I.
Maturation of Oocytes
continues at Puberty
In the diplotene,
homologous
chromosomes are
attached at chiasmata.
During childhood, most
Primary oocytes remain oocytes become atretic;
arrested in prophase and
do not finish their first
only approximately
meiotic division before 40,000 are present by
puberty is reached. This
arrested state is produced
the beginning of
by oocyte maturation puberty, and fewer than
inhibitor (OMI), a small 500 will be ovulated.
peptide secreted by
Near the time of birth, nofollicular cells
Oogonium is present,
600,000 to 800,000
oocytes are arrested in
the diplotene stage of
Prophase I.
Maturation of Oocytes
continues at Puberty
Each month,
15 to 20 follicles selected
from this pool begin to
mature, known as
preantral stage. Flat
follicular cells become
cuboidal and begin
secreting the zona
pellucida. By the end of
he preantral stage, the
follicular cells form
stratified layers of
granulosa cells.
Primary oocyte
is still in the
diplotene stage
Maturation of Oocytes
continues at Puberty
As follicles continue to grow, cells of the theca folliculi (Ovarian connective
tissue surrounding the developing oocyte) organize into an inner layer of Some of the maturing cells
secretory cells, the theca interna, and an outer fibrous capsule, the theca every month die, while
externa others begin to accumulate
fluid in a space called the
antrum, thereby entering
the antral or vesicular
stage.

Fluid continues to
accumulate such that,
immediately prior to
ovulation, follicles are quite
swollen and are called
mature vesicular follicles or
Primary oocyte
Graffian follicles
is still in the
diplotene stage
Maturation of Oocytes
continues at Puberty

perivitelline
space
Space bet. Primary oocyte
Zona is still in the
pellucida diplotene stage
and cell
a surge in luteinizing
membrane hormone (LH)
of the
secondary The cell then enters
oocyte meiosis II but
arrests in
metaphase
approximately 3
hours before
ovulation

Meiosis II is completed only if

the oocyte is fertilized;
otherwise, the cell degenerates
approximately 24 hours after
ovulation.
Morphological Changes During Maturation of Gametes

Spermatogenesis
Maturation of spermatogonium into
spermatozoa
Maturation of Spermatogenesis
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. Shortly before puberty, the sex Spermatogenesis
cord develops into the , which begins at
seminiferous tubules puberty,
includes all of the
events by which
spermatogonia
are transformed
into
spermatozoa.
PGCs give rise to
Spermatogonial stem cells.

PGCs give rise to Type A

spermatogonia, which undergo
series of mitosis.

At the end of the series, type A

spermatogonia give rise to Type B
spermatogonia, which then divides
to produce primary spermatocytes
Spermatogonial stem cells
give rise to spermatids
Primary spermatocytes then enter a
prolonged prophase I (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.

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
Spermiogenesis: Maturity
into Spermatozoa
(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.

(2) condensation of the nucleus;

(3) formation of neck, middle piece, and tail; and

(4) shedding of most of the cytoplasm

as residual bodies that are phagocytized by
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.
Abnormal Gametes
Some follicles may contain multiple
primary oocytes, which may give
rise to twins and triplets, but
majority of these cases degenerate
before maturation of oocyte.

Multinucleated follicles die before

maturity

10% of spermatozoa have

observable defects. Sperms with
morphologic abnormalities lack
normal motility and probably do
not fertilize oocytes
Laboratory Journal Article
Reporting
• Search for a journal article on recent advances or understandings about a
specific chromosomal aberration or abnormality.
• The research article should be a research article, not a blog or a review article.
• The article should be published in a journal with at least 5.
• Your report should be composed of the following:
o Title
o Introduction
o Methods
o Results and Discussion
o Conclusion
o 10 item Quiz
• Maximum of 20 minutes presentation, 10minutes Q&A, and 15mins Quiz.
Laboratory Journal Article
Reporting
Group Consultation Date Reporting Date
2 Nov 17 Nov 24
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8
6 Nov 18 Nov 25
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9
10 Dec 1 Dec 8
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1 Dec 9
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