Sexual Differentiation Flashcards
Define sexual determination
Genetically controlled process, dependent in the ‘switch’ on the Y chromosome (chromosomal determination of male or female).
Define sexual differentiation
The process by which internal and external genitalia develop as male or female.
Gonadal sex dev. explained (3)
SRY gene created the testis (in absence of Y chromosome, ovaries develop)
SRY switches on briefly during embryo dev. (>week 7) = gonad made into a testis (In absence, ovary is formed)
Products of testis (AMH, Testosterone) influence further gonadal and phenotypic sexual development.
What hormones do the testis produce?
Anti-Müllerian hormone(AMH) - Sertoli cells
Testosterone - Leydig cells
Mechanisms of SRY action (5)
SRY = DNA binding protein -> acts as a TF
Critical site of DNA binding is upstream of SOX9 (TF)
SOX9 works through a +tive feedback mechanism, it binds to its own upstream activation (= levels remain high, even if SRY declines)
SOX9 then acts to stim. expression of further downstream genes.
Becomes a Sertoli cell: SRY determines executive policy and SOX9 implements it
How does SOX9 achieve its effects?
1) stim. PGD2 production(pre-Sertoli cells) = acts as a paracrine hormone to stim. more SOX9 production in these cells! 2nd +tive feedback mechanism to re-inforce all precursors along Sertoli pathway.
2) stim. production of FGF9 = acts as chemotactic factor for cell migration in dev. testis, + further stim. production of SOX9! 3rd +tive feedback mechanism
3) stim. AMH production = regression of Müllerian ducts
4) inhibition of female TF’s WNT4 + FOXL2
Gonadal development - both (2)
After fertilisation, a pair of gonads develop, which are BIPOTENTIAL
Their precursor is derived from Genital Ridge Primordial(common somatic mesenchymal tissue precursors) - 3.5/4.5 wks! This is on posterior wall of lower thoracic lumbar region.
what 3 cell waves invade the Genital Ridge? (3)
3 waves of cells invade the genital ridge…
- Primordial Germ Cells – become Sperm (male) or Oocytes (female).
- Primitive Sex Cords – become Sertoli cells (male) or Granulosa cells (female).
- Mesonephric Cells – become blood vessels and Leydig cells (male) or Theca cells (female).
1) Primordial Germ Cell Migration
Initially: A small cluster of cells in the epithelium of yolk sac expands (by mitosis) @ around 3wks.
They then migrate to connective tissue of the hind gut -> the region of the dev. kidney -> onto genital ridge ~ completed by 6wks
2) Primitive sex cords (Sertoli/granulosa)
Cells from germinal epithelium (that overlies the genital ridge mesenchyme) migrate inwards as columns called primitive sex cords.
Picture
3) Mesonephric cells -men and women
Original in the mesonephric primordium (lateral to the genital ridges)
In males: act under influence of pre-Sertoli cells (which express SRY) to form:
Vascular tissue
Leydig cells ~ synthesise testo., don’t express SRY
Basement membrane ~ contribute to formation of seminiferous tubules + rete-testis
In females: w/o influence of SRY they form:
Vascular tissue
Theca cells
Gonadal sex summary
Images
Internal Reproductive Organs - all men are …, women are in the…(2)
Müllerian ducts:
Most important in female
Inhibited in male by AMH
Wolffish ducts:
Most important in the male stim. by testo.
Lack of stim. by testo. means regression in female
Internal sex differentiation
8mages
5-a-reductase - men AND NOT women (3)
Testo. converted to DHT by 5-a-reductase (in genital skin)
DHT binds to testo. receptor (more potent)
DHT causes: (differentiation of male external genitalia)
Clitoral area enlarges = penis
Labia fuse and become ruggated = scrotum
Prostate forms