Normal Sexual Differentiation Flashcards
Sexual Determination
Genetically controlled process dependent on the ‘switch’ on the Y chromosome.
Chromosomal determination of male & female.
Sexual Differentiation
The process by which internal and external genitalia develop as male or female
SRY gene creates ________
The testis
Absence of Y Chromosome
Ovaries
What is SRY (Sex Determining Region)
Transcription Factor
When does SRY switch on?
Switches briefly on during early development (>week7)
What does SRY switched on, make?
Gonad -> Testis -> Cells -> Hormones
Testis Develop and Form which two cells?
Sertoli and Leydig cells
Sertoli cells produce…
AMH (anti-mullarian hormone)
Leydig cells produce…
Testosterone
Picture of one chromosome:
Euchromatin and Heterochromatin
Pseudoatosomal Region
Mechanism of SRY action
SOX 9’s first positive feedback mechanism?
SOX9 can bind its own upstream activation site so its levels remain high even if SRY declines.
This is a positive feedback mechanism.
Mechanism of SRY action
SOX9 activation stimulates production of?
and by what?
Stimulates production of prostaglandin D2 (PGD2) by the pre-sertoli cells.
Mechanism of SRY action - How does SOX9 achieve its effects?
What does PGD2 act as?
Acts as a paracrine hormone to stimulate further SOX9 production in these cells.
Mechanism of SRY action - How does SOX9 achieve its effects?
SOX-9 stimulates production of?
SOX9 stimulates production of fibroblast growth factor 9 (FGF9).
Mechanism of SRY action - How does SOX9 achieve its effects?
FGF-9 acts as a _____
It further stimulates what?
FGF9 acts as a chemotactic factor for cell migration into the developing testis.
It also further stimulates the production of SOX9 a third positive feedback mechanism.
Mechanism of SRY action - How does SOX9 achieve its effects?
SOX-9 also stimulates production of?
anti-Mullerian hormone (AMH).
Mechanism of SRY action - How does SOX9 achieve its effects?
AMH causes the regression of the…⠀⠀⠀⠀⠀
mullerian ducts
which develop into the uterus and fallopian tubes in the female!
Mechanism of SRY action - How does SOX9 achieve its effects?
SOX9 inhibits the production of female transcription factors:⠀
Female Transcription Factors
WNT4 & FOXL2
Bipotential meaning
Gonads that can develop into either male or female
Where do the precursors of bipotential gonads come from? and what are they called?
common somatic mesenchymal tissue precursors called the genital ridge primordia
When approximately does this genital ridge primordia region appear?
(3½ - 4½ weeks)
Where is this anatomically located:
Common somatic mesenchymal tissue precursors called the genital ridge primordia
(3½ - 4½ weeks)
Posterior wall of lower thoracic lumbar region
Genital Ridge (3 waves of cells invade gential ridge)
1) Primordial Germ cells become either?
Sperm or Oocytes
Genital Ridge (3 waves of cells invade gential ridge)
1) How do Primordial Germ cells become sperm or oocytes?
- Small Cluster of cells in epithelium of yolk expand by mitosis (~3 weeks)
- They then migrate to:
*connective tissue of hind gut
*region of developing kidney
*onto Genital ridge waiting for signal
(completed by week 6)
Genital Ridge (3 waves of cells invade gential ridge)
2) Primitive Sex Cords become either?
Sertoli (male ) or Granulosa cells (female)
Genital Ridge (3 waves of cells invade gential ridge)
2) How are primative sex cords formed?
Cells from the germinal epithelium that overlied the genital ridge mesenchyme migrate inwards as columns called the primitive sex cords!
Genital Ridge (3 waves of cells invade gential ridge)
2) Male Summary
SRY expression
Penetrate medullary mesenchyme & surround primordial germ cells to form testis cords – precursor of seminiferous tubules.
Eventually become Sertoli Cells which express AMH.
Genital Ridge (3 waves of cells invade gential ridge)
2) Female Summary
No SRY
Sex cords ill defined and do not penetrate deeply
Instead, they condense in the cortex as small clusters around primordial germ cells – precursor of ovarian follicle
Eventually become Granulosa cells.
Genital Ridge (3 waves of cells invade gential ridge)
3) Mesonephric Cells become?
- Blood vessels
- Leydig cells (male)
- Theca cells (female).
Genital Ridge (3 waves of cells invade gential ridge)
3) Where do Mesonephric Cells originate from?
The mesonephric primordium which are just lateral to the genital ridges.
Genital Ridge (3 waves of cells invade gential ridge)
3) In males, Mesonephric Cells act under the influence of?
pre-sertoli cells (which themselves express SRY)
Genital Ridge (3 waves of cells invade gential ridge)
3) The pre-sertoli cells form 3 things, what are they?
- Vascular tissue
- Leydig cells (synthesize testosterone, do not express SRY)
- Basement membrane – contributing to formation of seminiferous tubules and rete-testis
Genital Ridge (3 waves of cells invade gential ridge)
3) In females, the cells without the influence of SRY they form:
- Vascular tissue
- Theca cells
Mullerian Duct will grow regardless unless?
Inhibited by AMH
Wollfian Duct is stimulated by?
Testosterone
Genital Ridge picture
Purple
Where is testosterone converted to DHT?
At the genital skin
What is the enzyme responsible for testosterone conversion into DHT?
5-a-reductase
What is Testosterone converted to in the genital skin?
Testosterone is converted in the genital skin to the more potent androgen DHT (dihydrotestosterone) by 5-a-reductase.
How does DHT causes differentiation of the male external genitalia? (Give specific examples)
- Clitoral area enlarges into penis
- Labia fuse and become ruggated to form scrotum
- Prostate forms
Sex differentiation summary
You got this!
Events in Sex Differentiation with Foetal age
What happens at week 4 Foetal age?
1) Wolfian Duct development
2) (Week ~4.5) Genital ridge
What happens at week 5 Foetal age?
Primordial Germ Cell migration
What happens at week 6 Foetal age?
Mullerian Duct development
What happens at week 7 Foetal age?
Seminiferous tubules
What happens at week 8 Foetal age?
-AMH made so Mullerian regress in male
-Leydig cells
What happens at week 9 Foetal age?
First signs of vagina
First meiotic prophase in oogonia
What happens at week 10 Foetal age?
Begin masculinisation of external genitalia
Prostatic buds
Begin regression of Wolffian Duct in female
Testis begins migration
What happens at week 12-14 Foetal age?
Penis developed
What happens at week 17 Foetal age?
First follicles
What happens at week 24 Foetal age?
Vagina developed