11. Sexual Differentiation

Question 1

sex determination

Answer 1

occurs at fertilisation

inheritance of X/Y from father

Question 2

3 main events in determining boy or girl

Answer 2

sex determination
differentiation of gonads
differentiation of internal and external genital organs

Question 3

gonad origin

Answer 3

week 2: primordial germ cells (PGCs) arise from epiblast = pluripotent
PGCs migrate to yolk sac
PGCs then return to genital ridge: become indifferent gonad

Question 4

gonad differentiation

Answer 4

at genital ridge
XX PGCs replicate at cortex
XY PGCs replicate at medulla

Question 5

gonad gender decision relies on

Answer 5

genetic switches

hormones

Question 6

genetic switches

Answer 6

general transcription factors (e.g. Wt1, Sf1)
specific promotors of testosterone development (e.g. Sry, Sox9)
specific promotors of ovarian development (e.g. (Wnt-4, FoxL2)

Question 7

fate of female gonad cell lines

Answer 7

PGCs - oogonia (primary oocytes)
sex cord cells - granulosa
cortex - layer of thecae cells (secrete androgens)

Question 8

fate of male gonad cell lines

Answer 8

PGCs - spermatogonia
Sry influences definition and identity of Sertoli cells - secrete AMH
AMH suppresses female development pathway and induces cells in intermediate mesoderm to become Leydig (secrete testosterone)

Question 9

kidney development origin

Answer 9

intermediate mesoderm (same as reproductive system)

Question 10

kidney development location

Answer 10

between somites and lateral playte (either side of aorta)

Question 11

3 stages of kidney development

Answer 11

ponephros - disappears soon after
mesonephros - leaves remnants
metanephros - become kidney

Question 12

development of internal genital organs

Answer 12

begin differentiation at ~8 weeks
formed from priori identical primordial structures
embryos of both sexes possess 2 sets of pairs

Question 13

internal organ development in female embryo

Answer 13

Müllerian duct is kept, due to absence of AMH

Müllerian duct becomes: oviduct, uterus, cervix, upper part of vagina

Question 14

internal organ development in male embryo

Answer 14

AMH causes Müllerian duct regression
testosterone promotes Wolffian duct differentiation
Wolffian duct becomes:
epididymis, vas deferens, seminal vesicle

Question 15

external genitals in both sexes

Answer 15

elevated midline swelling = genital tubercle 
tubercle consists of:
urethral groove 
paired urethral folds
paired labioscrotal swellings

Question 16

external genitals in male embryo

Answer 16

some testosterone is converted to DHT
DHT stimulates development of urethra, prostate and external genitals 
genital tubercle -> penis 
urethral folds fuse -> spongy urethra
labioscrotal swellings -> scrotum

Question 17

external genitals in female embryo

Answer 17

absence of DHT
genital tubercle -> clitoris 
urethral folds remain open -> labia minora
labioscrotal swellings -> labia majora
urethral groove -> vestibule

Question 18

abnormalities in sexual differentiation

Answer 18

chromosomal 
hermaphroditism 
gonadal dysfunction 
tract abnormalities 
gonadal descent 
external genitalia

Question 19

chromosomal abnormalities in sexual differentiation

Answer 19

Turner’s Syndrome

Klinefelter’s Syndrome

Question 20

Turner’s syndrome

Answer 20

monosomy: XO
1:2500 females
99% non viable embryos
survivors fail to sexually mature at puberty
several physical abnormalities

Question 21

signs/symptoms of Turner’s syndrome

Answer 21

low hairline
short stature
poor breast development 
small finger nails 
underdeveloped ovaries 
aortic coarctation 
no menstruation 
frown spots (nevi) 
widely spaced nipples 
shield shaped thorax

Question 22

Klinefelter’s syndrome

Answer 22

XXY
1:600-1000 male births
birth: appear normal 
become infertile 
exhibit some features associated with female development

Question 23

signs/symptoms of Klinefelter’s syndrome

Answer 23

taller than average 
reduced facial hair/male pattern hair growth 
breast development 
osteoporosis 
feminine fat distribution 
small testes (atrophy)

Question 24

hermaphroditism

Answer 24

true hermaphrodites
female pseudohermaphrodite
male pseudohermaphrodite

Question 25

true hermaphrodites

Answer 25

very rare
born with both ovarian and testicular tissue (ovotestis)
external genitalia may be ambiguous, or appear to be male/female
possible cause - 2 fertilised eggs fuse to form tetragametic chimera

Question 26

female pseudohermaphrodite

Answer 26

46 XX with virilisation - due to androgens
internal sex organs are normal
external appearance = male
features: fusion of labia, enlarged clitoris
may be caused by exposure to male hormones prior to birth

Question 27

male pseudohermaphrodite

Answer 27

46 XY with undervirilisation
external genitals: incompletely formed, ambiguous or female
features: blind-ending vagina, absence of breast development, amenorrhoea
testis: normal, malformed or absent
main causes = defective androgen synthesis or action

Question 28

androgen insensitivity syndrome (AIS)

Answer 28

testicular feminisation
1:20000-64000 male births
male hormones are normal
receptor is dysfunctional

Question 29

leydig cell hypoplasia

Answer 29

leydig cells do not secrete testosterone
(maybe insensitive to LH)
external genitalia = normally female/slightly ambiguous
no internal female genitalia develop (uterus)

Question 30

Swyer’s syndrome

Answer 30

gonadal dysfunction - XY gonadal dysgenesiys
associated with XY karyotype
caused by alteration to Sry gene
external appearance = female
non functional gonads (no testicular differentiation)
gonad may develop into malignancy

Question 31

tract abnormalities

Answer 31

uterine, eg. uricornuate uterus
vagina, eg. genesis
ductus deferens: unilateral or bilateral absence, failure fo mesonephric duct to differentiate

Question 32

cryptorchidism

Answer 32

may be unilateral/bilateral
occurs 30% premature, 3-4% full term males
descent may take place during year 1

Question 33

undescended ovaries

Answer 33

quite rare

detected in clinical fertility assessment

Question 34

male hypospadia

Answer 34

external genitalia abnormality
1:125 live male births
failure of male urogenital folds to fuse
outcome = proximally displaced urethral meatus