sexual differentiation

Question 1

describe the bipotential gonad

Answer 1

= equivalent to the formation of genital ridge

• arise as paired structures in intermediate mesoderm
• development of genital ridge dependent on the activation of nuclear transcription factors

Question 2

what genes allow the intermediate mesoderm to form the genital ridge

Answer 2

• WT-1 (-KTS)

- SF1

Question 3

male gonadal determination

Answer 3

SRY has been demonstrated as the initial gene determining male gonadal development

SRY stimulates SOX-9

• initial transcription by SF-1
• then markedly upregulated by SRY

SOX-9 once stimulated completes testicular differentiation and inhibits ovarian transcription factors also

Question 4

what inhibits SOX-9

Answer 4

beta-catenin

Question 5

FGF-9

Answer 5

crucial growth factor for male sex determination

• FGF-9 participates in both sex determination and testis differentiation

Question 6

2 main functions of the ovaries

Answer 6

• production of steroid hormone

- generation of mature oocytes capable of being fertilised

Question 7

initial development of internal genitalia

Answer 7

• develop from the wolffian and mullerian ducts

wolffian = epididymis, vas deferens, seminal vesicles

mullerian = fallopian tubes, uterus, upper 3rd vagina

Question 8

determination of the development of internal genitalia

Answer 8

• essentially determined by presence of leydig and sertoli cells
• testosterone stabilises wolffian structures
  - needs high local (testes) conc
• sertoli cells secrete AMH which regresses mullerian structures

essentially internal genitalia is determined by the presence of a testis
in the absence of a testis, mullerian structures will remain

Question 9

sertoli cells role in male internal genitalia

Answer 9

1. sertoli cells produce AMH by SF-1 (AMH gene)
2. AMH causes mullerian duct regression by binding to a AMH receptor

sertoli cells first to form in testis

Question 10

leydig cells role in male internal genitalia

Answer 10

1. leydig cells produce testosterone by SF-1 (steroid gene)

2. testosterone causes wolffian duct stabilisation by binding to an androgen receptor

Question 11

formation of male external genitalia

Answer 11

in the 1st trimester HCG and in the 2nd and 3rd trimester LH act on leydig cells. Leydig cells via a steroid gene SF-1 produces testosterone. Testosterone then gets converted to dihydrotestosterone via alpha-reductase. DHT exposure on genital tubercle is what forms male external genitalia via the binding of DHT to an androgen receptor

Question 12

formation of female genitalia

Answer 12

absence or complete resistance to androgen results in female external genitalia

absence of sertoli cells results in internal female genitalia

Question 13

causes of genetic testicular development problems

Answer 13

mutations in

• SRY
• SOX-9
• WT-1
• SF-1

Question 14

when does sex differentiation occur

Answer 14

gonads (bipotential <6 weeks)

internal genitalia ( bipotential <7 weeks)

external genitalia (bipotential <8 weeks)

Question 15

SRY

Answer 15

found solely in pre-sertoli cells in the testis
(activation procedes sertoli development)

initially = SOX-9 transcription by SF-1
later = SRY up-regulates SOX-9 to complete testicular differentiation

Question 16

FGF-9

Answer 16

• up-regulated by SOX-9 and also stimulates SOX-9
• inhibits ovarian transcription factors
• secreted by pre-sertoli cells
• enhances proliferation of SF-1 positive cells e.g. increased precursors of SRY
  - increases pre-sertoli cells

Question 17

what transcription factor allows the bipotential gonads to become ovaries

Answer 17

FOXL2