sexual differentiation and disorders Flashcards
What is sexual differentiation?
process by which internal and external genitalia develop as male or female
What initiates male sexual differentiation?
Sex determining region (SRY) gene on short arm of Y chromosome, acting as a transcription factor
Presence of SRY causes development of…
testis
Absence of SRY causes development of…
ovaries
What cells do testis develop?
Sertoli cells: produce AMH
Leydig cells: produce testosterone
What are Genital ridges?
bipotential cluster of cells in embryo
-can develop either testis or ovaries which are responsible for the differentiation of primordial germ cells into male/female gametes
What are the Cells invading genital ridge?
1) Primordial Germ Cells: become sperm or oocytes
2) Primitive Sex Cords: become Sertoli cells or Granulosa cells
3) Mesonephric Cells: become Leydig cells or Theca cells; also blood vessels
Describe the Action of primitive sex cords in males and females.
penetrate medullary mesenchyme deeply to form testis cords, which then become Sertoili cells in males
ill defined in females, therefore don’t penetrate deeply and condense in cortex around primordial germ cells to become Granulosa cells
What are Mullerian Ducts?
Embryonic ducts that can develop into female internal genitalia
What are Wolffian Ducts?
Embryonic ducts that can develop into male internal genitalia under stimulation by testosterone
How do males not develop mullerian ducts?
Mullerian ducts are inhibited by AMH (produced by Sertoli cells), hence they are regressed in males
How do females not develop Wolffian ducts?
Lack of stimulation by testosterone causes regression of Wolffian ducts in femlaes
What is external genitalia development influenced by?
Testosterone and dihydrotestosterone (DHT)
What is 5 alpha Reductase?
an enzyme that converts testosterone into dihydrotestosterone
- in genital skin
- present in both males and females
Describe the Male external differentiation
Conversion of testosterone to DHT by 5a Reductase:
- genital tubercle swells and becomes glans penis
- genital swelling swells up more to become scrotal swelling and then scrotum
- testes descend through inguinal canal into scrotum
- scrotum skin becomes ruggated
- urethral fold folds around urogenital membrane and becomes tube
Describe the Female external differentiation?.
5a Reductase present, but no testosterone, therefore no DHT produced, causing:
- genital tubercle becomes clitoris
- genital swellings enlarge and form labia majora
- urethral fold develops in labia minora
- urogenital membranes forms vestibule of vagina
What is Androgen Insensitivity Syndrome (AIS)?
A syndrome caused by a mutation of the androgen receptor gene that renders tissues insensitive to androgenic hormones like testosterone.
Affected XY individuals:
- external female genitalia due to absence of DHT
- testis form due to SRY gene presence
- regressed internal genitalia because AMH inhibit Mullerian ducts and no testosterone stimulation for Wolffian duct differentiation
What is 5-Alpha Reductase Deficiency?
Testosterone in XY individual can’t be converted to DHT:
- testes form due to SRY gene
- internal male genitalia due to AMH inhibiting Mullerian Ducts and stimulation of Wolffian Ducts by testosterone
- external female genitalia because no DHT
What is Turner Syndrome?
Female genetic condition with one X chromosome (XO)
- ovaries develop (no SRY gene)
- Internal female genitalia because no AMH for Mullerian duct development and lack of testosterone prevents Wolffian duct differentiation
- external female genitalia
What is the Effect of one X chromosome (Turner Syndrome) on ovaries?
Ovarian dysgenesis (streak ovaries)
What is Congenital Adrenal Hyperplasia?
XX female exposed to high levels of androgens in utero
Progestogens (in gonads) can be converted to cortisol and aldosterone (in adrenal glands) by 21a hydroxylase
Defect/Deficiency in 21a hydroxylase causes:
- no cortisol/aldosterone produced therefore more progestogens
- no negative feedback via HPA axis, increase in CRH and ACTH
- ACTH upregulates P40scc enzyme to force more cholesterol into steroid synthesis pathway
- progestogens converted to androgens (high testosterone)
> Internal female genitalia (no AMH) development of Mullerian ducts
> not internal male genitalia because androgen levels not high enough to rescue Wolffian ducts
- external male genitalia (high DHT)
- PHIV
