Sexual differentiation

Question 1

Genetic sex

Answer 1

• XX = female, XY = male
• True hermaphrodite = XX and XY
• Male pseudohermaphrodite = XY but phenotypically female
• Female pseudohermaphrodite = XX but phenotypically male

Question 2

Development of gonads and internal ducts 1

Answer 2

• Gonads arise bilaterally near the developing adrenal glands
• In an XX individual the cortex grows and the medulla atrophies, leading to ovary formation
• In an XY individual the cortex atrophies and the medulla grows, leading to testis formation
• The critical gene is SRY (located on Y chrom), and presence of SRY induces testi formation (w/o SRY the default is ovary formation)
• Early on the fetus has both wolffian and mullein ducts
• If there are testis developing the testis (leydig cells) produce T and DHT (needed mostly for prostate growth) which retain/develop the wolffian ducts (masculinization)

Question 3

Development of gonads and internal ducts 2

Answer 3

• Inhibition of the mullerian ducts (defeminization) occurs from the developing testis producing anti-mullerian hormone (AMH, from sertoli cells)
• If there are ovaries there is no T/DHT/AMH produced and thus the wolffian ducts degenerate (demasculinization) and the mullerian ducts are retained (feminization)
• Wolffian ducts give rise to epididymis, vas deferens, seminal vesicles and prostate
• Mullerian ducts give rise to fallopian tubes, uterus, and proximal 1/3rd of vagina

Question 4

Development of external genitalia 1

Answer 4

• Determining which kind of external genitalia to develop depends on whether or not DHT is present (DHT present-> male, not present-> female)
• Genital tubercle: develops into glans of penis or glans of clitoris, and shaft of penis or shaft of clitoris
• Urethral fold: develops into the penile raphe and labia minora

Question 5

Development of external genitalia 2

Answer 5

• Genital swellings (labio-scrotal folds): form the scrotum and labia majora
• This development requires active 5-a reductase in the primordial external genitalia, and failure to have this results in female external genitalia no matter the genotype (and vice versa)
• Testosterone is important for developing the internal duct structures (DHT for prostate), DHT responsible for the external genitalia development

Question 6

Sex chromosome aneuploidy

Answer 6

• Both due to non-disjunction somewhere in meiosis of either gametes
• Turner’s syndrome (45, XO): female phenotype, ovaries degenerate early on leaving infertility, but have nl reproductive tract
• Klinefelter’s syndrome (47, XXY): male phenotype, limited gonadal development leads to infertility (low T levels-> bone problems)

Question 7

D/o in synthesis/metabolism/receptors of steroid hormones 1

Answer 7

• Congenital adrenal hyperplasia (XX): phenotype variable due to overproduction of androgens by adrenals, are capable of fertility
• 5a reductase def (XY): initially female phenotype, male phenotype at puberty
• Amount of DHT produced not enough to sufficiently masculinize the external genitalia (until puberty)
• Often can find testes in labia majora

Question 8

D/o in synthesis/metabolism/receptors of steroid hormones 2

Answer 8

• Androgen insensitivity (XY): phenotype female, inability to bind T leads to degeneration of wolffian duct
• Still make AMH so no mullerian duct (no reproductive tract)
• Testes remain in abd and produce T which gets aromatized to E2-> female phenotype (unable to be fertile but can retain female sex characteristics via OCPs)