Sex Development 2 Flashcards
Describe the known roles of genes in gonadal differentiation, particularly SF1, DAX, AMH, SOX9, and SRY.
1
Q
Describe the role of SF1.
A
- One of the earliest acting genes in reproductive tract development
- Affects all three levels of the hypothalamic-pituitary-gonadal axis
-
Regulates other genes:
- ACTH receptor
- LH
- AMH
-
Mutations suggest dosage effects
- homozygous - gonadal dysgenesis and adrenal insufficiency
- heterozygous - gonadal dysgenesis without adrenal insufficiency
2
Q
Describe the role of SRY.
A
- Testes-determining factor
-
Specific roles
- induces Sertoli cell differentiation
- migration of mesonephric cells into the genital ridge
- proliferation of cells in the genital ridge
- male-specific vasculature
- Sex reversal in 46, XX males with SRY and 46, XY females without SRY
3
Q
Describe the role of SOX9.
A
-
Sex-determining factor
- upregulated after SRY
- expressed in Sertolic cells
- regulates AMH
- Induces chondrogenesis
- Haploinsufficiency leads to XY gonadal dysgenesis (male to female sex reversal and campomelic dysplasia
4
Q
Describe the role of DAXI.
A
- Dose-sensitive sex reversal
- Adrenal Hypoplasia Congenita Locus on Chromosome X, Gene I
-
Expressed in:
- hypothalamus
- pituitary
- testis
- adrenal cortex
- ovary
- Human duplication → 46, XY sex reversal
-
Human deletion:
- adrenal hypoplasia congenita
- hypogonadotropic hypogonadism
- may also have impaired spermatogenesis
5
Q
Describe the role of WNT 4.**
A
- Expressed early and involved in gonad development
-
Balanced opposition model
-
Female
- mullerian duct formation
- maintain oocytes in cortex
- suppress Leydig cell development in ovary
-
Male
- proper testis vasculature
- organization of sex cords
-
Female
- Heterozygous human WNT4 mutations seen in 46, XX females with Mayer-Rokitansky-Kuster-Hauser syndrome (absent mullerian structures)
- mild virilization and increased androgen concentrations
6
Q
Describe the role of AMH.
A
- Antimullerian hormone
- Produced by Sertoli cells
- Regulated by SF1 and SOX9
- Causes regression of mullerian strucutres
- Paracrine effects - AMH from testis causes regression on ipsilateral side
- Also produced in:
- late gestation
- after birth
- adulthood
- Mutation found in 46, XY individuals with persistent mullerian duct syndrome