Sexual Differentiation And Disorders Flashcards
What is sexual determination?
A genetically controlled process which is dependant on the Y chromosome ‘switch’
What is sexual differentiation?
The process by which internal and external genetalia develop as male or female
What are the steps in sexual differentiation?
Genotypic sex, gonadal sex, phenotypic sex, legal sex
What are the names of the ducts that turn into the male internal genetalia?
Wolffian
What are the names of the ducts that turn into the female internal genetalia?
Mullarian
What is the gonadal precursor derived from?
Common somatic mesenchymal tissue precursors (called genital ridge pomadia)
Where is the genital ridge pomadia found?
Posterior wall of the lower thoracic lumbar region
What are the three waves of cells that form the genital ridge?
Primordial germ cells, primitive sex cords and mesonephric cells
What do the primordial germ cells differentiate into?
Sperm (male) or oocytes (female)
What do the primitive sex cords differentiate into?
Sertoli cells (male) or granulosa cells (female)
What do mesonephric cells differentiate into?
Blood vessels and leydig cells (male) or theca cells (female)
What happens in primordial germ cell migration?
A small cluster of cells in the epithelium of the yolk sac expands and migrates to the connective tissue of the hindgut by 6 weeks
How are the primitive sex cords formed?
Cells from the germinal epithelium that overhangs the genital ridge - the mesenchyme migrate inwards as columns
What are the features of male primitive sex cords?
They express SRY, penetrate medullary mesenchyme and surround primordial germ cells to form testis cords.
Eventually become Sertoli cells which express AMH
What are the male primitive sex cords precursors to?
Seminiferous tubules
What are the features of female primitive sex cords?
No SRY, they condense in the cortex around the primordial germ cells (precursor to ovarian follicles)
Eventually become granulosa cells
Where do the mesonephric cells originate?
Mesonephric primordium - just lateral to the genital ridges
What do the mesonephric cells form in females?
Vascular tissue and theca cells
What do the mesonephric cells form in males?
Vascular tissues, leydig cells, basement membrane
What do leydig cells do?
Synthesise testosterone and don’t express SRY
What does the basement membrane in males contribute to?
Formation of seminiferous tubules and rete-testis
What inhibits mullarian duct Development in males?
AMH (anti-mullarian hormone)
What do Mullerian ducts form in females?
Uterine tubes, the uterus and part of the vagina
What inhibits wolffian duct development in females?
Lack of testosterone stimulation
What do the wolffian ducts form in males?
Epididymis and vas deferens
What enzyme converts testosterone into dihydrotestosterone?
5-alpha reductase
Why is testosterone converted into dihydrotestosterone?
It’s much more potent
What does dihydrotestosterone cause?
Differentiation of the male external genetalia:
- clitoral area enlarges into penis
- labia fuse and become ruggated to form scrotum and the prostate forms
What is gonadal dysgenesis?
Sexual differentiation is incomplete
What causes gonadal dysgenesis?
Missing SRY in male or partial or complete loss of the second X chromosome in females
What does intersex mean?
Have some components of both tracts or ambiguous genetalia
What are the symptoms of androgen insensitivity syndrome?
Testes form and make AMH so the mullarian ducts regress, but there’s no differentiation of the wolffian ducts - means female or ambiguous external genetalia
What is the phenotype in complete androgen insensitivity syndrome?
Completely female - due to undescended testes
How do you diagnose complete androgen insensitivity syndrome?
Primary amenorrhoea/ lack of body hair
Ultrasound and karyotype
What is the phenotype of partial androgen insensitivity syndrome?
Varying degrees of penile and scrotal development from ambiguous genetalia to a large clitoris
What is the external phenotype in 5-alpha reductase deficiency?
Feminine or ambiguous external genetalia
What is the internal phenotype in 5-alpha reductase deficiency?
Undescended testes, but no dihydrotestosterone so no penile or scrotal formation
Do patients with a 5-alpha reductase deficiency have wolffian or mullarian ducts?
Wolffian ducts
What may happen at puberty in patients with a 5-alpha reductase deficiency?
High testosterone levels may induce virilisation
What causes Turner syndrome?
No Y chromosome or second X chromosome
What is the phenotype of a patient with Turner syndrome (internal and external)?
Ovaries, mullarian ducts, female external genetalia
What are the symptoms of Turner’s syndrome?
Failure of ovarian function (may be fertile - mosaicism)
Uterus and uterine tubes are present but small
May have brittle bones (hormones support bone formation/ maturation)
What is the phenotype of congenital adrenal hyperplasia?
Masculinised external genetalia but female internal genetalia
