Sexual differentiation: how to make a boy or girl Flashcards
Sex determination
Sex is determined at fertilisation
Inheritance of X/Y from father
Gonad origin
At week 2 primordial germ cells arise from the epiblast
They are pluripotent
Migrate to yolk sac stalk to avoid becoming imprinted
Later return, travelling to the genital ridge and becoming the indifferent gonad
Primordial germ cells at the genital ridge
XX PGCs replicate at cortex
XY PGCs replicate at the medulla
Gonad gender decision relies on
Genetic switches
Hormones
Genetic switches
General transcription factors
Specific promoters of testis development
Specific promoters of ovarian development
Fate of female PGCs
Oogonia
Fate of sex cord cells
Granulosa
Fate of cortex
Layer of thecal cells
Secret androgens before those generated by the follicles
Fate of PGCs
Spermatogonia
Kidney development
Origin: intermediate mesoderm
Where: between the somites and lateral plate
3 stages of kidney development
Pronephros
- disappears soon after
Mesonephros
- leaves remnants
Metanephros
- becomes kidney
Mesonephros
Middle stage of kidney development
Leaves behind ducts that become integral part of the reproductive system
Internal genital organs
Begin differentiation at about week 8, formed from identical primordium structures
Embryos of both sexes possess two sets of paired ducts at the start
- paramesonephric
- mesonephric
Mullerian duct female
Paramesonephric
In female embryo duct is kept due to absence of AMH
Mullerian duct
- oviduct
- uterus
- cervix
- upper part of the vagina
Mullerian duct male
In male embryo
- AMH causes mullerian duct regression
- testosterone promotes wolffian duct differentiation
Wolffian duct
Mesonephric
Wolffian duct
- epididymis
- vas deferens
- seminal vesicle
External genital organs
At first embryos of both sexes show an elevated midline swelling- genital tubercle
Tubercle consists:
- urethral groove
- paired urethral folds
- paired labioscrotal swellings
Development of male external genital organs
Some testosterone is converted into dihydrotestosterone
DHT stimulates development of the urethra, prostate and external genitals (scrotum and penis)
Genital tubercle –> penis
Fusion of urethral folds –> spongy urethra
Labioscrotal swellings –> scrotum
Development of female external genital organs
Absence of DHT
Genital tubercle –> clitoris
Urethral folds remain open –> labia minora
Labioscrotal swellings –> labia majora
Urethral groove –> vestibule
Abnormalities
Chromosomal
Hermaphroditism
Gonadal dysfunction
Tract abnormalities
Gonadal descent
External genitalia
Turner’s Syndrome
Monosomy, XO
1:2500 females (does not affect males)
99% non-viable embryos
Survivors fail to sexually mature at puberty
Exhibit several physical abnormalities
Diagnosis confirmed through amniocentesis
Physical abnormalities of Turner’s syndrome
Short stature
Low hairline
Shield shaped thorax
Widely spaced nipples
Shortened metacarpal
Small finger nails
Characteristic facial features
Constriction of aorta
Poor breast development
Elbow deformity
Rudimentary ovaries
No menstruation
Klinefelter’s Syndrome
47, XXY
1:600-1000 male births (does not affect females)
Birth appear normal (undetected
Become infertile
Exhibit some features associated with female development (e.g. gynaecomastia)
Diagnosis confirmed through amniocentesis
Physical abnormalities of Klinefelters syndrome
Taller than average height
Reduced facial hair
Reduced body hair
Breast development
Osteoporosis
Feminine fat distribution
Small testes
True hermaphroditism
Extremely rare
Born with body ovarian and testicular tissue
46XX (SRY), 45X (SRY) and 45X
Possible cause e.g. two ova fertilised by two sperm that fuse to form a tetragametic chimera
External genitals may be ambiguous or appear to be female or male
Female pseudohermaphrodite
46, XX with virilisation (due to androgens`0
Internal sex organs are normal
External appearance and genital: male
Features:
- fusion of labia
- enlarged clitoris
Possible cause: exposure to male hormones prior to birth
Male pseudohermaphrodite
46, XY with undervirilisation
External genitals: incompletely formed, ambiguous or clearly female
Some features: blind ending vagina, absence of breast development, primary amenorrhoea
Testis: normal, malformed or absent
Main causes
- defective androgen synthesis
- defective androgen action
Androgen insensitivity syndrome
aka testicular feminisation
Affects 1:20000-64000 male births
Male hormones are normal
Dysfunctional receptor to these hormones
Leydig cell hypoplasia
Leydig cells do not secrete testosterone
Possible reason: body insensitive to LH
External genitalia normally female/ slightly ambiguous
No female internal genitalia develop
Gonadal dysfunction
e.g. XY gonadal dysgenesis (Swyer’s Syndrome)
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
Tract abnormalities
Uterine: e.g. unicornuate uterus
Vagina: e.g. agenesis
Ductus deferens: unilateral or bilateral absence, failure of mesonephric duct to differentiate
Gonadal descent
More apparent and common in males than on females
Cryptorchidism
May be unilateral/ bilateral
Occurs 30% premature; 3-4% males
Descent may take place during year 1
Undescended ovaries
Quite rare
Detected in clinical fertility assessment
Male hypospadia
1:125 live male births
Failure of male urogenital folds to fuse
Outcome: proximally displaced urethral meatus
The brain and behaviour
What makes us a boy or girl: sexual behaviour
Gender identity from gene expression, given the correlation between inactivation of genes from the X chromosome and predisposition to transexualism
