Sexual Differentiation

Question 1

What is sexual determination? (2)

Answer 1

Genetically controlled process dependent on a ‘switch’ on the Y chromosome
Chromosomal determination of male or female

Question 2

What is sexual differentiation? (1)

Answer 2

Process by which internal & external genitalia develop as male or female

Question 3

What are gender & sexual identity? (5)

Answer 3

Genotypic sex (XX or XY)
Gonadal sex (ovaries or testes)
Phenotypic sex (external shape & features)
Legal sex (passport, marriage, titles)
Gender identity (unrelated to others categories, how the person feels about themselves)

Question 4

What is psychosexual neutrality? (2)

Answer 4

The view that gender assignment of newborn with ambiguous genitalia can be made regardless of the endocrine history

Question 5

What is neural bias? (2)

Answer 5

The ideas that a tendency for male or female is already present in neonates
As a result of prenatal factors e.g. hormonal milieu in utero

Question 6

What is SRY (sex-determining region of the Y chromosome)? (5)

Answer 6

DNA binding protein that acts as a TF
SRY gene creates the testis
In absence of Y chr, ovaries develop
SRY switches on briefly during embryo development (~wk7)
Testis cells differentiate into Sertoli cells (producing AMH) & Leydig cells (producing testosterone)
These influence further gonadal & phenotypic sexual development

Question 7

Explain the actions of SRY & SOX9 (7)

Answer 7

The critical site of DNA binding is upstream of SOX9 (also a TF)
SOX9 can bind to its own upstream activation site so its levels remain high even if SRY declines (+ve feedback)
SOX9 stimulates expression of further downstream genes
- stimulates PGD2 production by pre-Sertoli cells (paracrine hormone, stimulates further SOX9 production)
- stimulates production of FGF9 (chemotactic factor for cell migration into the developing testes)
- stimulates production of AMH
SOX9 also inhibits female TFs -(WNT4 & FOXL2)

Question 8

What are the gonads like after fertilisation? (2)

Answer 8

After fertilisation the gonads are bipotential

Arise from common somatic mesenchmyal tissue precursors on the genital ridge

Question 9

Which three waves of cells invade the genital ridge? (6)

Answer 9

1. Primordial germ cells (become spermatozoa or oocytes)
   - small cluster of cells expand population by mitosis in the epithelium of the yolk sack and migrate to the genital ridge
2. Primitive sex cords (become Sertoli cells or Granulosa cells)
   - cells from germinal epithelium overlying the genital ridge that migrate inwards to form columns
3. Mesonephric cells (become BVs & either Leydig cells or Theca cells)
   - originate in the mesonephric primordium

Question 10

How does male internal genitalia develop? (4)

Answer 10

1. PGS become spermatozoa
2. PSCs - SRY expression is restricted to these cells which proliferate & penetrate the medullary mesenchyme & surround the PGCs
   - form testis cords & eventually become Sertoli cells which express AMH (cause M-duct to regress)
3. MCs - pre-Sertoli cells expressing SRY cause formation of vascular tissue, Leydig cells & basement membrane (for seminiferous tubules & rete-testis)

Question 11

How does female internal genitalia develop? (5)

Answer 11

1. PGCs become oocytes
2. PSCs - no SRY expression. Sex chords are ill-defined & do not penetrate deeply. Condex in the cortex as small clusters around the PGCs
3. MCs - in absence of SRY, vascular tissue & Theca cells (which synthesis androstendione, the substrate for Granulosa cells to produces oestradiol using aromatase) form

Question 12

What are the Mullerian duct & the Wolffian duct precursors of? (2)

Answer 12

Mullerian duct = precursor to uterus, fallopian tubes & upper 3rd of the vagina
Wolffian duct = precursor or epididymis, seminal vesicles, vas def & ejaculatory ducts

SRY causes testosterone (stimulating W-duct development) & AMH (causing regression of M-duct) production (by Leydig & Sertoli cells)

Question 13

By what mechanism does male external differentiation occur? (5)

Answer 13

Testosterone is converted in the genital skin to dihydrotestosterone (DHT) by 5-a-reductase (type II)
DHT also binds to test. receptor but is more potent & more stable when bound to receptor
Causes (in week 10-24):
- enlargement of clitoris to penis
- labia fuse & become ruggated to form scrotum
- prostate forms

Question 14

By what mechanism does female external differentiation occur? (2)

Answer 14

Lack of androgen leaves the vagina, labia & clitoris to develop (week 9-24)

Question 15

What is the historical view of gender classification? (2)

Answer 15

Presence/absence of penis/vagina has generally assumed to predict all other gender features to be concordantly male/female
Bipolar physiological classification has been paralleled by bipolar allocation of psychosocial traits & gender attributes (based on attitudes/behaviours)

Question 16

What is meant by transexual/transgender? (1)

Answer 16

Individuals who feel their gender identity is at variance with their assigned gender

Question 17

What experiments have been conducted for bipolar classification based on behavioural/cognitive functions? (4)

Answer 17

Dog/rodent experiments - androgens may influence the development of sexually distinct behaviours by acting on brain structure in utero
Rodent studies - male courtship behaviour & mounting as well as female lordosis
Tx of female mice with test. in first 5 days of lie - increases display of masculine sexual behaviour & decreases female pattenr
Castration of male rates during same period removes influence of androgens & has reverse effect

Question 18

What are the morphological & functional differences in human brain structure b/w sexes? (3)

Answer 18

Neuroimaging
Morphological sex differences in amygdala (emotional processing) & hippocampus (memory & learning)
Functional MRI shows difference b/w females & males in phonological processing - detects changes in blood oxygenation & flow in response to neural activity0

Question 19

What is the effect of gender assignment at birth? (4)

Answer 19

Some gendered patterns may be induced by the way boys & girls are treated/as a result of the of expectations by others
Children appear to be more rigidly gender stereotyping than adults
By age 5 children appear to have a sense of gender constancy
Gender stereotypes are applied to babies & children use/apply them from an early age

Question 20

What is meant by gonadal dysgenesis? (3)

Answer 20

Incomplete sexual differentiation
Usually missing SRY in male or partial/complete deletion of second X in female
Abnormal development of the gonads

Question 21

What is meant by sex reversal? (1)

Answer 21

Phenotype does not match genotype

Question 22

What is meant by intersex? (2)

Answer 22

Ambiguous genitalia or components of both tracts

Difficult to determine sex of infant

Question 23

What is AIS? ()

Answer 23

Androgen insensitivity syndrome
XY individual produces test. but this has no effect
No/insensitive test. receptors (due to mutations, >300)
Male karyotype + high circulating androgen levels
Testes visible on ultrasound (undescended)