Normal Sexual Differentiation Flashcards
What is sexual determination?
- Genetically controlled process dependent on the ‘switch’ on the Y chromosome.
- Chromosomal determination of male or female.
What is sexual differentiation?
The process by which internal and external genitalia develop as male or female.
What is the SRY gene?
- Sex determining region
- Only found on the Y chromosome
- Switches on briefly during embryo development to turn the gonad into testis
- Ovaries develop in its absence
Which cells are developed in the testis and what hormones do they produce?
- Sertoli cells -> make anti-Mullarian hormone (AMH)
- Leydig cells -> make testosterone
Where in the testis are Leydig and Sertoli cells found?
- Sertoli cells are found in the seminiferous tubules
- Leydig cells are found adjacent to the seminiferous tubulues
What happens when SRY is activated
- SRY is a DNA binding protein that acts as a transcription factor
- SRY turns off many ovarian genes and turns on testicular genes
- It binds upstream of itself, it’s a transcription factor for itself
- The site of DNA binding is upstream of SOX9 which is also a transcription factor.
- SOX9 can bind its own upstream activation site so its levels remain high even if SRY declines. This is a positive feedback mechanism.
- SOX9 turns off a lot of ovarian genes and turns on many testicular genes
- SOX9 then acts to stimulate the expression of further downstream genes.
- Both SRY and SOX9 are essential for the development of sertoli cells
How does SOX9 achieve its effects?
- Stimulates production of prostaglandin D2 (PGD2) by the pre-sertoli cells. PGD2 acts as a paracrine hormone to stimulate further SOX9 production in these cells. This second positive feedback mechanism serves to re-enforce all precursor cells along the sertoli pathway.
- SOX9 stimulates production of fibroblast growth factor 9 (FGF9). 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.
- SOX9 stimulates the production of anti-Mullerian hormone (AMH).
- Inhibition of female transcription factors WNT4 and FOXL2
What are the effects of activation of SOX9?
- Positive feedback pathway for itself
- Cause the development of sertoli cells from precursor cells
- Inhibition of WNT4 and FOXL2 (female transcription factors)
- Cell migration into developing testis
- Stimulate the production of AMH
What are gonads after fertilisation?
Bipotential
Where are the gonads derived from?
They are derived from the genital ridge primordia on posterior wall of lower thoracic lumbar region.
What do genital ridge’s become?
Testis or ovaries
What do the Mullerian and Wolffian ducts form?
- Mullerian ducts becomes the uterine tubes and the upper 3rd of the vagina
- Wolffian ducts becomes the vas deferens and the internal genitalia connecting the testis to the urethra
What 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).
Describe primordial germ cell migration.
- An initially small cluster of cells in the epithelium of the yolk sac expands by mitosis at around 3 weeks.
- They then migrate to the connective tissue of the hind gut, to the region of the developing kidney and on to the genital ridge – completed by 6 weeks.
Describe how primitive sex cords invade the genital ridge
- Cells from the germinal epithelium that overlies the genital ridge mesenchyme migrate inwards as columns called the primitive sex cords
