15. Genetics, Sex and Gender

Question 1

Sex chromosomal abnormalities

Answer 1

• X: turner’s (50% fertile)
• XXX: mild growth retardation, reduced intelligence
• XXY: Klinefelters: taller, youthful, gynecomastia, reduced fertility
• XYY: tomboyish, taller

Question 2

Androgeny/hemophrodism

Answer 2

• Sex: possessing both male and female reproductive organs
• Gender: possesing both male and female qualities or feelings/identity
• True: both ovaries and testis
• Pseudo: presence of both sexes at different stages of life

Question 3

Male Gonadal development

Answer 3

• Genetic factors initiate process that directs the indifferent gonads toward testis development
• Activation of Sertoli cells (sustentacular cells) to produce Mullerian inhibiting hormone (MIH) causing Mullerian duct degeneration
• Stimulation of Leydig cells (interstitial cells) to secrete testosterone, which then directs development of the Wolffian duct towards epididymis, vas deferens and seminal vesicles
  
  • Testosterone conversion to dihydrotestosterone (DHT)
  • Direct development of urethra, prostate gland and penis
    No testosterone: Wolfian duct degenerates spontaneously
    Y chromosome

Question 4

Y chromosome

Answer 4

• Short, internal repeats allow self-recombination
• Produces Testis Determination Factor (TDF)
• SRY (TDF) is a transcription factor that via a molecular cascade activates Sertoli and Leydig cells
• Acts together with an autosomal genes
• Sox9 binds promoter of MIH
• SRY/SOX9 induce FGF9: chemotactic factor for primordial germ cells to penetrate gonadal ridge
• Induction of steroidogenesis factor 1 (SF1): stimulates differentiation of Sertoli and Leydig cells
• SF1 stimulates Leydig cells to make enzymes for testosterone production (from cholesterol)

Question 5

Male abnormal development

Answer 5

• Congenital Adrenal Hyperplasia (CAH
  
  • Genetic defect leading to excessive production of androgens
  • Androgens cause virilization of external genitals
• Effect of castration and testosterone-absence/presence on adult male and female behavior
• SRY mutation
  
  • XY female
  • No testis: no testis determination factor
  • No ovaries either (oogenesis needs other autosomal and X-chromosome factors)
  • Wolfian duct fails to develop (progesterone)
  • Internal and external genitals appear female, infertile, but able to carry child to term by embryo transfer
  • Defect rose during spermatogenesis
  • Hormones (estrogens) are necessary to induce breast formation and menstruation (no eggs)
• Inactivated X
• DHT converting enzyme
  
  • External structures lack due to lack of 5a-reductase; development (initially) as female-like, internal structures are male
• Androgen insensitivity (AIS)
  
  • Genetic males with female phenotype
  • Gonadal sex correct → gonads differentiate to testis
  • Produce MIH - females duct system has degenerated
  • Produce testosterone and DHT but no receptor to “see” these hormones
  • Cannot respond to androgen surge at puberty because testosterone and DHT use the same receptor
  • Puberty: breast development, but no menstruation
  • Partial or complete depends on type of mutation