1. Genetic determination of the sex Marie Černá
Lecture No 504-V

2. 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 ( )

3. Meiosis

4. Prophase of Meiosis I Leptotene – chromosome condensation
Zygotene – chromosome synapse → bivalent
Pachytene – chromatid tetrad, crossing-over
Diplotene – chiasmata
Diakinesis – chromosome segregation

6. Gamete maturation

7. 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

9. 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

11. Spermatogenesis Oogenesis
spermatogonia ↓
primary spermatocytes
secondary spermatocytes
spermatids
spermatozoa
oogonia ↓
primary oocytes
secondary oocytes
fertilized egg (zygote)
mitosis
meiosis I
meiosis II

14. Barr body

15. 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

16. The sex is estimated: Genetic determination → GONADS → hormones
Hormonal differentiation →
genital ducts, external genital + brain
Psychological differentiation →
self-determination

17. Early development paired indifferent gonad
in the 5th week of pregnancy
up to 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

18. 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

19. 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

20. 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

21. 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

22. Traits Sex-limited 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

25. Turner syndrome

26. Turner syndrome

27. Turner syndrome

28. Klinefelter syndrome

29. Klinefelter syndrome

30. Klinefelter syndrome

31. 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)

32. 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

33. 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

34. 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

35. 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

36. Congenital adrenal hyperplasia

37. 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

38. DNA is the most stable molecule of our body
queen Nefertiti
1381 – 1344 B.C.
secret room in the tomb of Amenhotepa II
in Kings’ valley in Luxor

39. 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

40. 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