Download Meiosis

Genetic determination of the
sex
Marie Černá
Lecture No 504-V
Meiosis – reconstruction
of genetic material
• Rearrangement of chromosomes on
the basis of crossing-over
• Chance segregation of maternal and
paternal chromosomes into gametes
– combination number 223 (8 388 608)
Meiosis
Prophase
of Meiosis I
1.
2.
3.
4.
5.
Leptotene – chromosome condensation
Zygotene – chromosome synapse → bivalent
Pachytene – chromatid tetrad, crossing-over
Diplotene – chiasmata
Diakinesis – chromosome segregation
Gamete maturation
Male meiosis - spermatogenesis
• is initiated during puberty by androgens
• takes about 64 days
• includes spermiogenesis
conversion of spermatids into functional spermatozoa:
- formation of the acrosome
- nucleus condensation and cytoplasm shedding
- formation of the neck, midpiece and tail
Female meiosis - oogenesis
• dictyotene state – in the fetus at 12 – 20 weeks
division of the primary oocytes stops
at diplotene of prophase of Meiosis I
• ovulation - from puberty to menopause
the secondary oocyte is shed into the uterine tube →
division of the secondary oocytes stops
at metaphase of Meiosis II
• fertilization - entry of a sperm the ovum
the end of Meiosis II
Spermatogenesis
Oogenesis
spermatogonia
oogonia
mitosis
↓
↓
primary spermatocytes
primary oocytes
↓
↓
meiosis I
secondary spermatocytes
secondary oocytes
↓
↓
meiosis II
spermatids
fertilized egg (zygote)
↓
spermatozoa
Barr body
Sex determination
• in mammals (humans),
some insects (fruit flies)
• in some insects
(grasshoppers, crickets, roaches)
• in birds, some fishes,
some insects (butterflies, moths)
• in bees and ants
The sex is estimated:
• Genetic determination →
GONADS → hormones
• Hormonal differentiation →
genital ducts, external genital + brain
• Psychological differentiation →
self-determination
Early development
paired indifferent gonad
• in the 5th week of pregnancy
• up to 2 000 primordial germ cells from
the endoderm of the yolk sac infiltrate
the primitive sex cords within
the mesodermal genital ridges, which are
developments of the coelomic epithelium
Further development without
presence of the Y chromosome
• the primitive sex cords break down
• proliferation of the epithelial cortical cords
• oestrogens, from the maternal system,
placenta and fetal ovaries, →
the paramesonephric Műllerian ducts develop
→ the uterine tubes and uterus
the mesonephric Wolffian ducts regress
differentiation of the external genitalia
The SRY gene on the Y chromosome
• in the 7th week „zinc finger protein“ is activated
• leads to proliferation in the testis cords:
- Leydig cells from mesenchyme →
androgens (testosterone) →
the mesonephric Wolffian ducts develop
→ vas deferens and epididymis
- Sertoli cells from epithelium, in the 4th month
→ Műllerian inhibiting substance (MIS) →
the paramesonephric Műllerian ducts regress
The SRY gene on the Y chromosome
• production of androgens (testosterone) →
• in the 8th – 18th week (until the 4th month)
differentiation of the external genitalia
testosterone under action of local 5-α-reductase
converts to dihydrotestosterone
• in the 7th month of pregnancy
contraction of the gubernaculum
– descent of the testis into the scrotum
Puberty is triggered by
hormones secreted by the pituitary gland:
• Adrenal glands → androgens (androsterone) →
pubic and axillary hair in girls
• Ovaries → oestrogens → breast growth,
menstruation, uterus matur., pelvis broadening
• Testes → enlargement of the testes
→ androgens (testosterone) →
penis and larynx growth, spermatogenesis
Sex-limited
Traits
Sex-influenced
both are encoded by genes on autosomes
expressed in only
one sex secondary sexual
characteristics
level of their expression
is different in different
sex - early baldness
as an autosomal
dominant trait in men
Turner syndrome
Turner syndrome
Turner syndrome
Klinefelter syndrome
Klinefelter syndrome
Klinefelter syndrome
Chromosome Y
• Pseudoautosomal homologous regions
at the distal ends of short (Xp and Yp) and
long (Xq and Yq) arms of sex chromosomes
→ homologous recombination in meiosis I
• SRY gene on short arm Yp,
determines male sex (gonads - testes)
• AZF regions on long arm Yq, determine
development of male gametes (sperms)
Disorders of Sex Determination
due to Mutation of SRY Gene
Male phenotype with karyotype 46,XX can be
caused by abnormal presence of SRY gene:
• SRY gene is transferred to X chromosome
during abnormal crossing-over out of
homologous regions of X and Y chromosomes
• SRY gene is transferred to autosome by
translocation
Disorders of Sex Determination
due to Mutation of SRY Gene
Female phenotype with karyotype 46,XY can be
caused by missing of SRY gene:
• SRY gene is deleted
• SRY gene is mutated
Disorders of
Gonadal and Sexual Development
• hermaphroditism – presence of
both ovarian and testicular tissue
→ the genitalia are ambiguous
• pseudohermaphroditism – presence of
gonadal tissue of only one sex
but with ambiguous or opposite
external genitalia
Female pseudohermaphroditism
46,XX karyotypes → normal ovaries, but
male external genitalia
Congenital adrenal hyperplasia
- autosomal recessive disorder
- deficiency of 21-hydroxylase
of the adrenal cortex
- ↓ cortisol + aldosteron, ↑ androgens
Congenital adrenal hyperplasia
Male pseudohermaphroditism
46,XY karyotypes → normal testes, but
female external genitalia
Deficiency of the steroid 5-α-reductase
- autosomal recessive disorder
Androgen insensitivity syndrome
- X-linked syndrome of testicular feminization
- mutations of the androgen receptor gene
DNA is the most stable molecule
of our body
secret room in the tomb of Amenhotepa II
in Kings’ valley in Luxor
queen Nefertiti
1381 – 1344 B.C.
Literature
Genetics in Medicine,
sixth edition, revised reprint
Thompson & Thompson
Saunders, 2004
Chapter 2: Chromosomal Basis of Heredity
Human Gametogenesis and Fertilization
pages 12 – 16
Chapter 10: Clinical Cytogenetics
The Sex Chromosomes and Their Abnormalities
pages 165 – 179
Clinical Case Studies: 27, 32
Literature
Medical Genetics at a Glance, second edition,
Dorian J. Pritchard & Bruce R. Korf
Blackwell Publishing, 2008
Part 1: Developmental biology 10,(11,12),13
Part 2: Medical genetics 23, 25
pages 28 – 35, 59 – 61, 64 – 65