Sexual Differentiation: How to make a boy or girl

Question 1

Where do primordial germ cells originate?

Answer 1

Arise from epiblast week 2

-PGCs are pluripotent

Question 2

Differentiation of PGCs

Answer 2

1. MIgrate to yolk sac to prevent becoming imprinted

2, Later returns next to genital ridge (next to kidneys) and become the indifferent gonad

XX replicate at cortex
XY replicate at medulla

Gender decisions is dependant on genetic switches and hormones

Question 3

Genetic switches

-all

Answer 3

General transcription factors
-Wt1, Sf1

Specific promoters of testis development
-Sry, Sox9

Specific promoters of ovarian development
-Wnt-4, FoxL2

Question 4

Specific promoters of testis development

Answer 4

Sry

Sox9

Question 5

Specific promoters of ovarian development

Answer 5

Wnt-4

FoxL2

Question 6

Supporting precursor cells

Answer 6

Urogenital ridge>Bipotential gonad

Supporting cell precusors develop into

• Follicular cells in ovaries
• Seroli cells in testis

Question 7

Primordial germ cells develop into?

Answer 7

Oocytes in ovaries

Pro-spermatogonia in testis

Question 8

Steroidogenic precursors develop into?

Answer 8

Develop into internal theca cells in ovaries

Leydig cells in testis

Question 9

Outline the differentiation of the

• Female PGCs
• Sex cord cells
• Cortex

Answer 9

Female PGCs => oogonia (primary oocytes)

Sex cord cells => granulosa (support and nutrifying the ovum)

Cortex => layer of thecal cells => secrete androgens before those generated by the follicles

Question 10

Sry

Answer 10

Specific genetic promoter of testis development

Influences definition and identity of Sertoli cells

Stimulates AMH secretion

Question 11

AMH

Answer 11

Anti-mullerian hormone

Produced from sertoli cells under Sry gene stimulation

• Suppresses female development pathway
• Induces Leydig differentiation (from intermediate mesoderm)

Question 12

Where do the kidneys originate?

Answer 12

intermediate mesoderm (as the reproductive organs)

between somites and lateral plate (each side of the aorta)

Question 13

Outline the 3 stages of development of the kidneys

Answer 13

• Pronephros - disappears soon after
• Mesonephros - leaves remnants and ducts that become integral to development of reproductive organs
• Metanephros - becomes kidney

Question 14

When do internal genital organs begin differentiation?

Answer 14

Week 8

Question 15

Female pseudohermaphrodite

• description
• cause

Answer 15

46 XX female with virilization
internally they are female, with male external genitals

Features: enlarged clit, fusion of labia

possibly due to exposure of male hormone prior to birth e.g in congenital virilizing adrenal hyperplasia

Question 16

True hermaphrodite

Answer 16

Both ovaries and testis (fused)

Question 17

Male pseudohermaphrodite

• description
• cause
• features

Answer 17

46 XY male with undervirilization

external genitalia- ambiguous or female
testis can be underdeveloped, normal or absent

Cause- defective androgen synthesis
defective androgen action (e.g receptor dysfunction)

features- no breast development, primary amenorrhea, blind ending vagina

Question 18

Male pseudohermaphrodite

-types of conditions

Answer 18

• Androgen insensitivity syndrome

- leydig cells HYpoplasia (body insensitive to LH)

Question 19

Gonadal dysfunction

-XY gonadal dysgenesis, a.k.a. Swyer’s Syndrome

Answer 19

Associated with XY karyotype

Cause: alteration to Sry gene

External appearance: female (no menstruation)

No functional gonads (no testicular differentiation)

Gonad may develop into malignancy

Question 20

Tract abnormalities

-examples

Answer 20

uterine (unicornuate uterus)
Vagina agenesis
Ductus Deferens: unilateral or bilateral absence, failure of mesonephric duct to differentiate

Question 21

What duct develops into female internal genital organs?

Answer 21

Paramesonephric duct

Question 22

What duct develops into male internal genital organs?

Answer 22

Mesonephric duct

Question 23

Gonadal descent

Answer 23

undescended ovaries in females
-detected in fertility assessments

cryptorchidism- hidden tests (common in premature babies 30%)

Question 24

What is male hypospadia?

Answer 24

external genitalia problem where there is failure of urogenital folds to fuse
leads to proximal displaced urethral meatus

Question 25

What structure is produced by the fusion of the urethral folds in the male?

Answer 25

The spongy urethra

Question 26

What structure forms in the female when the urethral folds remain open?

Answer 26

labia minora

Question 27

What structure forms in female when labioscrotal swellings remain open?

Answer 27

labia majora

Question 28

When does differentiation of gonads occur?

Answer 28

Week 5

Question 29

When does differentiation of internal and external genital organs occur?

Answer 29

after week 5

Question 30

Where are ovaries derived from?

Answer 30

XX PGCs replicate at cortex

Question 31

Where are testes derived from?

Answer 31

XY PGCs replicate at medulla