W11 L1 Tues sex chromosome and determination 2

Question 1

Hypospadias, what is it and the rate

Answer 1

Ectopic placement of urethral opening
* Most common birth defect
* Affects 1/125 live male births in Victoria
* Increased by 50% in past 40 years – and still 1% PA in WA

Question 2

Cause for hypospadias

Answer 2

• Low T
• Excess E
• Early androgen priming
• Surgical repair
• Endocrine Disruption

Question 3

Discordance of phenotypic sex and possible cause

Answer 3

• can be hermaphroditism or pseudohermaphroditism
  -AMH or AMH receptor inadequacy
  -defect in steroid o genesis or androgen action

Question 4

What is testicular descent

Answer 4

• testes migrate (descend) from abdomen to scrotum via inguinal canal
• androgens, INSL3 and AMH from testes
• CGRP from the genitofemoral nerve
• scrotal location à 2-3°C cooler
• failure of descent (cryptorchidism)
• no sperm production
• high risk of testicular cancer

Question 5

Persistent Müllerian duct syndrome

Answer 5

-rare, affect XY
-autosomal recessive mutation in AMH or AMH receptor
-lead to crytorchid (most of the time)

Question 6

Congenital adrenal hyperplasia

Answer 6

• Autosomal recessive inheritance
• Defect in 21-hydroxylase gene (P450c21)
• Reduced cortisol and aldosterone (\ ­ ACTH )
• Increased adrenal androgen secretion
• Affected female foetus is masculinized
• But phenotype is intersex
• Genital surgery ® female appearance but brain seX ( huge problem)

Question 7

Complete androgen insensitivity cause and identification

Answer 7

• XY karyotype (SRY positive)
• AR gene mutation usually detected (allows carrier
  identification, prenatal diagnosis)
• Adult blood levels: high LH and T, slightly high FSH.
• Oestradiol level higher than normal male, less than adult female

Question 8

Complete androgen insensitivity characteristic

Answer 8

-tall (compare to female, normal male height) with normal breast (female) development
-absent or sparse body hair
-no uterus
-short vagina
-abdomianl testes

Question 9

5a-reductase deficiency

Answer 9

Clinical: Present as females at birth
*Puberty – masculinization of body, clitoral enlargement, male pattern body hair
-5a reductase mutation > no DHT, at puberty, there is enough testosterone to drive male development`

Question 10

Male brain development

Answer 10

• aromatase enzyme in many brain areas (only affects males during development)
• non-aromatisable androgens like DHT do not have same effect on brain as testosterone
• oestrogens masculinise brain
• anti-oestrogens can block some effects of T on brain sex
• effects via cell divisions in some cells and apoptosis in others

Question 11

Differences in male and female brain

Answer 11

location of the sexually dimorphic nucleus in the preoptic area (SDN POA) and the anteroventral- periventricular nucleus of the POA (AVPv-POA) of the rat
-male SDN-POA > female (behaviour?)
-male AVPv-SDN < female (LH surge?)

Question 12

Development of gender idendity

Answer 12

3 stages:
-Gender identity: 1-3 yrs
-Gender stability: 3 - 4 yrs
-Gender constancy: 5 - 6 yrs
Gender identity is distinct from homosexuality (men still identify as men; women as women)

Question 13

Link between homosexuality and older brother

Answer 13

• Best established influence in sexual orientation research
• fraternal birth order effect.
• Each additional older brother increases odds of
  homosexuality by 33%
• Effect restricted to biological older brothers, and not the number of older brothers you grows up with.
• Only true for right-handed homosexual men
• Confirms sexual orientation sex before birth

Question 14

Gender dysphoria

Answer 14

Different from homosexuality where men still identify as men; women as women. The cognitive/ brain sex is different from biological sex
-transsexuality
-gender idendity disorder
-hormone & sex reassignment surgery
-gender variant issue

Question 15

Brain Sex beyond hormones

Answer 15

• Thickness of the parietal cortex, male copulatory behaviors and social investigation behavior, males (i.e., testes-bearing animals) were masculine and females (i.e., ovaries-bearing animals) were feminine = hormones not chromosomes….. BUT there are some behavior coded by chromosome !
• XY-SRY had a higher, more masculine density of vasopressin fibers in the lateral septum.
• When midbrain mesencephalic embryonic neurons were grown in vitro, XY cultures were shown to develop more dopaminegic neurons than XX cultures – regardless of SRY.
• Sex chromosome complement influenced two sexually dimorphic social behaviors: intruder-directed aggression (higher in XY) and pup retrieval (higher in xx)