11. Sexual Differentiation Flashcards
sex determination
occurs at fertilisation
inheritance of X/Y from father
3 main events in determining boy or girl
sex determination
differentiation of gonads
differentiation of internal and external genital organs
gonad origin
week 2: primordial germ cells (PGCs) arise from epiblast = pluripotent
PGCs migrate to yolk sac
PGCs then return to genital ridge: become indifferent gonad
gonad differentiation
at genital ridge
XX PGCs replicate at cortex
XY PGCs replicate at medulla
gonad gender decision relies on
genetic switches
hormones
genetic switches
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)
fate of female gonad cell lines
PGCs - oogonia (primary oocytes)
sex cord cells - granulosa
cortex - layer of thecae cells (secrete androgens)
fate of male gonad cell lines
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)
kidney development origin
intermediate mesoderm (same as reproductive system)
kidney development location
between somites and lateral playte (either side of aorta)
3 stages of kidney development
ponephros - disappears soon after
mesonephros - leaves remnants
metanephros - become kidney
development of internal genital organs
begin differentiation at ~8 weeks
formed from priori identical primordial structures
embryos of both sexes possess 2 sets of pairs
internal organ development in female embryo
Müllerian duct is kept, due to absence of AMH
Müllerian duct becomes: oviduct, uterus, cervix, upper part of vagina
internal organ development in male embryo
AMH causes Müllerian duct regression
testosterone promotes Wolffian duct differentiation
Wolffian duct becomes:
epididymis, vas deferens, seminal vesicle
external genitals in both sexes
elevated midline swelling = genital tubercle tubercle consists of: urethral groove paired urethral folds paired labioscrotal swellings
external genitals in male embryo
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
external genitals in female embryo
absence of DHT genital tubercle -> clitoris urethral folds remain open -> labia minora labioscrotal swellings -> labia majora urethral groove -> vestibule
abnormalities in sexual differentiation
chromosomal hermaphroditism gonadal dysfunction tract abnormalities gonadal descent external genitalia
chromosomal abnormalities in sexual differentiation
Turner’s Syndrome
Klinefelter’s Syndrome
Turner’s syndrome
monosomy: XO
1:2500 females
99% non viable embryos
survivors fail to sexually mature at puberty
several physical abnormalities
signs/symptoms of Turner’s syndrome
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
Klinefelter’s syndrome
XXY 1:600-1000 male births birth: appear normal become infertile exhibit some features associated with female development
signs/symptoms of Klinefelter’s syndrome
taller than average reduced facial hair/male pattern hair growth breast development osteoporosis feminine fat distribution small testes (atrophy)
hermaphroditism
true hermaphrodites
female pseudohermaphrodite
male pseudohermaphrodite
true hermaphrodites
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
female pseudohermaphrodite
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
male pseudohermaphrodite
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
androgen insensitivity syndrome (AIS)
testicular feminisation
1:20000-64000 male births
male hormones are normal
receptor is dysfunctional
leydig cell hypoplasia
leydig cells do not secrete testosterone
(maybe insensitive to LH)
external genitalia = normally female/slightly ambiguous
no internal female genitalia develop (uterus)
Swyer’s syndrome
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
tract abnormalities
uterine, eg. uricornuate uterus
vagina, eg. genesis
ductus deferens: unilateral or bilateral absence, failure fo mesonephric duct to differentiate
cryptorchidism
may be unilateral/bilateral
occurs 30% premature, 3-4% full term males
descent may take place during year 1
undescended ovaries
quite rare
detected in clinical fertility assessment
male hypospadia
external genitalia abnormality
1:125 live male births
failure of male urogenital folds to fuse
outcome = proximally displaced urethral meatus
