In male embryo - AMH causes mullerian duct regression - testosterone promotes wolffian duct differentiation

Sexual differentiation: how to make a boy or girl Flashcards by Holly O'Flanagan

Sex determination

Sex is determined at fertilisation

Inheritance of X/Y from father

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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

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Primordial germ cells at the genital ridge

XX PGCs replicate at cortex

XY PGCs replicate at the medulla

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Gonad gender decision relies on

Genetic switches

Hormones

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Genetic switches

General transcription factors

Specific promoters of testis development

Specific promoters of ovarian development

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Fate of female PGCs

Oogonia

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Fate of sex cord cells

Granulosa

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Fate of cortex

Layer of thecal cells

Secret androgens before those generated by the follicles

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Fate of PGCs

Spermatogonia

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Kidney development

Origin: intermediate mesoderm

Where: between the somites and lateral plate

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3 stages of kidney development

Pronephros
- disappears soon after

Mesonephros
- leaves remnants

Metanephros
- becomes kidney

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Mesonephros

Middle stage of kidney development

Leaves behind ducts that become integral part of the reproductive system

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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

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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

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Mullerian duct male

In male embryo

AMH causes mullerian duct regression
testosterone promotes wolffian duct differentiation

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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