Sex differentiation Flashcards
3 parts of bi-potential gonad
Pronephros - caudal end forms adrenal glands
Mesonephros - forms gonads and internal reproductive structures
Metanephros - forms the kidneys
What determines if you become M or F?
Testes
Development of internal male genitalia.
Sertoli cells develop first - Secrete anti mullerian hormone which causes the regression fo female internal reproductive organs.
Leydig cells - Produce large amount of testosterone which promote wolffian duct stabilisation. NEED BOTH LEYDIG AND SERTOLI.
Development of external genitalia
In first trimester there is no pituitary development so no LH/FSH to stimulate leydig cell androgen/testosterone secretion.
hCG is an analogue for LH and stimulates testosterone release from first trimester.
Testosterone is then converted to dihydrotestosterone via 5a reductase.
DHT is more potent than testosterone and stimulates male external genitalia development.
Important hormones in bipotential gonad development
WT1 / Wills tumor 1
- Critical in development of genital ridge
SF1 / Steroidogenic factor 1
- Found through out all levels of sexual differentiation
- Hypothalamus, androgen receptors
Major contributors to male gonadal differentiation
SRY - Sex determining region of Y chromosome
- Stimulates SOX-9
- Found solely in the pre-sertoli cells of the testis
- SRY is activated causing development of sertoli cells which develops first.
SOX 9 - transcription factor which induces testes development from genital ridge ALSO inhibits b catenin from inducing ovarian development
FGF-9: Stimulates pre sertoli cell formation
SF- 1
What “completes” male gonadal determination?
SRY activating SOX-9 as it starts a cascade.
Increasing SOX-9:
1) Up regulates itself
2) Stimulates production of Prostaglandin D2 which is released paracrine and autocrinely further stimulating SOX-9 and sertoli cell maturation
3) Stimulates FGF-9 - cause pre sertoli cell development
Ovarian determination
FOXL2 - Promotes ovary formation from genital ridge
Beta catenin - inhibits SOX9 and SRY
Gonadal determination through out life
There’s shown to be constant inhibition of sexual differential hormones through out life.
Removal of FOXL2 in adult mice showed ovaries starting to develop testicular functionq
What does it mean if baby has uterus
NO TESTES - As sertoli cells are regulator of internal genitalia differentiation (produce AMH which regresses mullerian duct progression)
Where problems that occur in abnormalities of external male genitalia development.
Androgen receptor - Most common
5a reductase - Converts T in to DHT
Steroid genes
What are the two main tests for assesing suxal ambiguity at birth
- Karyotype
2. USS - uterus?
Common causes of undervirilised males
LH receptor mutation Steroid synthesis defect Androgen receptor mutation Often associated with small phallus or hypospadias Hypothalamus defect
SOX 9 deficiency symptoms
Campomelic dysplasia
XY female with short limbs would indicate this the cause of an external and internal female with male karyotype.
Wilms tumor 1 deficiency
No formation of genital ridge therefore ovaries
Renal problems as no renal development
