Ambiguous Genitalia

Question 1

Genitalia of embryo at 6 weeks

Answer 1

Undifferentiated gonads

Mullerian ducts

Wolffian ducts

Undifferentiated external genitalia

Question 2

What can be developed from Mullerian ducts?

Answer 2

Uterus

Fallopian tubes

Upper vagina

Question 3

What can be developed from Wolffian ducts?

Answer 3

Epididymis

Vas deferens

Seminal vesicles

Question 4

If Y chromosome is present, What does happen to genitalia after 6 weeks?

Answer 4

Undifferentiated gonads >>> Testes >>> produces testosterone & MIF (Mullerian inhibiting factor)

• MIF acts upon Mullerian ducts >>> Mullerian duct regresses
• Testosterone acts upon Wolffian ducts >>> develops into epididymis, vas deferens, seminal vesicles
• Testosterone turns into dehydro-testosterone >>> acts upon undifferentiated external genitalia >>> develops into male genitalia

Question 5

Which enzyme does convert testosterone to dehydrotestosterone?

Answer 5

5-alpha reductase

Question 6

If Y chromosome is absent, What does happen to genitalia after 6 weeks?

Answer 6

Undifferentiated gonads >>> ovaries >>> NO MIF & NO testosterone

• Due to lack of testosterone >>> Wolffian ducts regress
• Due to lack of MIF >>> nothing to inhibit Mullerian ducts >>> Mullerian ducts turn into uterus, fallopian tubes, uuper vagina
• By default: undifferentiated external genitalia >>> turns into female genitalia

Question 7

Divisions of ambigous genitalia

Answer 7

• Undermusculinisation of a male foetus (46, XY)
• Musculinisation of a female foetus (46, XX)
• Mosaicism of a cell line containing a Y chromosome & another that does not (45X or 46XY mosaic)

Question 8

Causes of undermusculinised male foetus (46, XY)

Answer 8

• Partial testicular failure
• Partial androgen insensitivity
• 5-alpha reductase deficiency
• Rare forms of CAH (Congenital adrenal hyperplasia)

e.g. 3beta-hydroxylase

17alpha-hydroxylase

• Rare syndromes: Smith-Lemil-Opitz (AR)

Question 9

Causes of musculinised female foetus (46, XX)

Answer 9

• External androgens, e,g, OCP ​
• Endogenous androgens, e.g.

1. Common forms of CAH (Congenital adrenal hyperplasia)

• ​21-hydroxylase
• 11-beta hydroxylase

​2. Virilising tumours

Question 10

Examples of abnormal chromosome/mosaicism

Answer 10

45X

46XY mosaic

Question 11

Appearence of genitalia in case of complete testicular failure

Answer 11

Normal female genitalia

Question 12

Appearence of genitalia in case of complete androgen insensitivity (= testicular feminisation syndrome)

Answer 12

Normal female genitalia