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
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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
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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
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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
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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
  • Heterozygous human WNT4 mutations seen in 46, XX females with Mayer-Rokitansky-Kuster-Hauser syndrome (absent mullerian structures)
    • mild virilization and increased androgen concentrations
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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
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