Sexual Differentiation: internal and External Genitalia differentiation Flashcards
What do internal genital ducts develop from?
The Wolffian and Mullerian Ducts
Wolffian or mesophric ducts form the internal male genitalia (epididymus, vas deferens, seminal vesicles)
Mullerian or paramesonephric ducts form the female internal genitalia (form as an invagination of the wolffian ducts) (fallopian tubes, uterus and upper 1/3 vagina)
How do you differentiate from Bipotential Internal genitalia to male or female?
Internal Genitalia are determined by the presence of a testis
If you have a testis:
- Sertoli cells release AntiMullerian Hormone (AMH) → Regresses Female structure
- Active Leydig cells produce Testosterone → Maintain Male structure
- Require testosterone receptors to maintain a high amount
No testis= no AMH, no testosterone → female structures
What happens if you had a testis on one side and ovary on the other, and why?
The hormones (AMH and Testosterone) work via local diffusion as there’s no blood vessels/circulation in the fetus.
Therefore on testis side you keep your wolffian structures (AMH and TEST. present) and lose femal structures → testis on 1 side
On ovary side no testosterone so you lose wolffian structure but maintain Mullerian structures as there’s no AMH (hemiuterus)
Draw this out, you should know this easily
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*SF-1 is a very important transcription factor
What will a loss of function in a gene critical to forming AMH or its receptor cause in a male?
No AMH > no uterus regression
The boy will also have a uterus!
Persistant Mullerian Duct Sydrome: Rentention of Mullerian structures (uterus, fallopian tubes) in an XY male.
Often associated with bilateral cryptorchidism. (
What happens if you lose function of a gene critical in the synthesis of testosterone in a male?
eg “androgen insensitive syndrome” (makes T, but is resistant to it)
No testosterone → no maintenence of male structures
The boys still makes AMH, so will not have male OR female internal genitalia.
But as there’s no T/DHT → female external genitalia
What will result in development of male or female External Genitalia?
Male results if: the genital tubercle is exposed to high concentrations of DHT (not just testosterone)
Lower concentrations/partial insensitivity to androgens → partial virilisation (small penis or large clitoris)
Female Results if: there’s absence or complete resistance to androgen
If testosterone, more specifically DHT is required for male virilisation, BUT the fetus has not yet developed a pituitary gland to have LH stimulate the Leydig cells, what stimulates to Leydig cells to produce Testosterone??
HCG in placenta (in 1sttrim) stimulates leydig cells to make large portions of testosterone (via SF-1 and steroid genes)
Pituitary LH in the 2nd and 3rd trimester then takes over (this requires LH receptors on Leydig)
If no pituitary, it will only start to form → micropenis
BUT Testosterone is only strong enough to control internal genitalia, so what reaction needs to occur?
Testosterone → Dihydrotestosterone (DHT)
Via enxyme 5a reductase
This bind much stronger to your androgen receptor!
whats the development of Labioscrotal swellings, urethral glands and Glans in Male vs Female at 12 weeks
12 Weeks: depends on testosterone
Labioscrtoal swellings:
Female → labia majora (thick skin)
Male → Scrotumskin (thin, rugated)
Urethral folds:
Female → labia minora
Male → the fallace of the penis
Glans:
female → clitoris
Male → glans penis
Prader Staging of Virilization
Grades external genitalia from normal female → normal male
Inbetween depends on levels of androgen exposure giving different levels of virilisation.
eg; initially you have hyperspadia (urethral opening at the shaft of the penis), so if this has occured there is abnormal virilisation
A loss of function of 5a reductase will cause?
A Undervirilised male genitalia; this can be from completely female genitalia → hypospadias
But at puberty you begin to produce huge amounts of androgens → sudden virilisation at puberty; they change sex!
Summary
The development of a testis usually determines __________
Female internal genitalia occurs in the abscense of ________
Female external External genitalia occurs in the abscense of ______
Make int/ext genitalia require _________ to be maintained
If a ______ doesn’t form the resulting int/ext sex will be female
The development of a testis usually determines male internal/external genitalia
Female internal genitalia occurs in the abscense of AMH (from Sertoli cells, if a uterus is present via US, there’s NO sertoli cells)
Female external External genitalia occurs in the abscense of the androgen effect
Make int/ext genitalia require androgen effect to be maintained
If a testis doesn’t form the resulting int/ext sex will be female
In assessing sexual ambiguity at birth, what tests do you do and how?
- Karyotype
- Pelvic USS (do they have a uterus?!)
USS can accurately determine female genitalia (uterus/cervix) as this is large at birht (Babies been swimming in maternal oestrogens)
A palpable gonad is almonst always a testis
Virilised female!
(XX, normal female internal genitalia, ovaries)
This means you’ve been exposed to androgens prenatally
- Fetal:*
- *Congenital sdrenal hyperplasia:** can’t make cortisol so you make androgen instead
Maternal:
Ingestion
Severe PCOS
Androgen secreting tumour (rare)
No uterus, so there are Sertoli cells there to produce AMH, therefore there is a testis present
This is a XY male but its likely a LOF of testosterone production or lLOF in androgen receptors.
- Leydig Cell Hypoplasia (LH receptor defect)
- Testosterone Synthesis Defects
- StAR (moves cholesterol into cell past mitochonfrial membranes to make hormones)
- CYP11A1
- CYP17
- 17B hydroxysteroid dehydrogenase
- Testosterone action defects
- 5a reductase
- Androgen Receptor (androgen insensitivity Syndrome)
Pubic hair from adrenal glands not gonads.
No TESTIS as there’s a uterus , so the defect is forming gonadal ridge or testis (high up, before you get a testis).
Possible mutation: SRY, SOX-9, WT-1, SF-1 (everything involved in forming testis)
Wilms Tumour 1
