Intro repro Flashcards
Sexual determination
genetically controlled process dependent on ‘switch’ on Y chromosome – chromosomal determination of male/female
Sexual differentiation:
internal + external genitalia develop as male/female process
Where is SRY gene
sex determining region on Y chromosome
SRY gene
switches ON week 7 so gonad –> testis
What cells does testis develop
Sertoli cells
Leydig cells
Sertoli cells
produce AMH
Leydig cells
produce testosterone
AMH
Anti Mullerian Hormone
inhibits Mullerian ducts, via apoptosis of Mullerian ducts – regresses
Gonad precursors
Mesenchymal tissue
Genital ridge
Where genital ridge
posterior thoracic-lumbar region
Mullerian duct
- females - to produce internal female organs
Wolffian ducts
- males - to produce internal male organs
Cell types which invade into genital ridge forming gonad?
- Primordial cells -
- Primitive sex cords
- Mesonephric cells
Primordial cells male/female
precursors of gametes
male = spermatogonia/spermatozoa
female = oogonia
Primitive sex cords male/female
form
male = Sertoli cells - SRY + AMH
female = granulosa cells
Mesonephric cells
form
male = leydig
female = theca cells
Describe route of primordial cells
- in clusters in yolk sac’s epithelial
- week 3 divide via mitosis + migrate via connective tissue of hind gut to genital ridge
Describe route of primitive sex cords
- on epithelium that overlie genital ridge
- primordial cells colonise ridge
- migrate into ridge in columns
Male sexual determination? (Step by step)
- SRY is present due to the presence of the Y chromosome
- Sex cords penetrate deep into mesenchyme
- Surround primordial cells forming testis cord
- Turn into sertoli cells - release AMH degenerating mullerian ducts
Female sexual determination? (Step by step)
- No Y chromosome
- Sex cords ill-defined
- Don’t penetrate deeply into mesenchyme
- Condense into cortex as small clusters surrounding primordial cells
- Form granulosa cells
- Absense of androgens dengerates Wolffian ducts
Origin of mesonephric cells
Originate from Mesonephric primordium lateral to genital ridge
Describe route of mesonephric cells
-some mesonephric cells migrate to genital ridge
-act as “Androgen secreting cells”
Males - under influence of pre-sertoli cells forming testosterone
Females - vascular tissues - Theca cells synthesises androgens
internal male
- Vas deferens
- Seminal vesicles
- Prostate
- Epididymis
internal female
- 1/3 top of the vagina
- Fallopian tubes
- Cervix
- Uterus
Male sexual differentiation? (Step by step)
- Gonads develop at genital ridge level in thoraco-lumbar region
- Testerone + AMH (from sertoli + leydig cells) degenerate Mullerian ducts
- Wollfian duct develops - Seminal vesicles, prostate, epididymis, vas deferens
Female sexual differentiation? (Step by step)
- Gonads develop into ovaries
- No AMH + testosterone, mullerian ducts grow - uterus, uterine tubes, cervix, upper 1/3rd of vagina
- Wollfian ducts regress
Dihydrotestosterone (DHT)
Hormone for male external genitalia
- Clitoral area –> penis
- Labia fuses + ruggated –> scrotum
- Prostate forms
Where’s 5 α-reductase
genital skin
5 α-reductase
Adds a hydrogen molecule to testosterone –> POTENT DHT
Identical features male/female before differentiation
- Urethral fold
- Genital swelling
- Genital tubercle
How does the presence of DHT affect the genital tubercle?
phallus of the penis
How does the presence of DHT affect the urethral ford?
Folds together forming hallow tube –> shaft of penis.
What happens to the genital swelling in the absence of DHT?
forms labia majora + minora
What happens to the urethral fold in the absence of DHT?
forms vaginal opening
What happens to the genital tubercle in the absence of DHT?
forms clitoris
Gonadal dysgenesis
incomplete sexual differentiation, missing SRY in male or partial/complete deletion of 2nd X in female – describes abnormal development of gonads
Sex reversal:
phenotype doesn’t match genotype
Intersex
have components of both tracts or ambiguous genitalia – sex of infant difficult to determine
Cause of AIS (Androgen Insensitivity Syndrome)?
Testosterone production via sertoli cells BUT undetected due to:
Mutated testosterone receptor
Error in signalling pathway
AIS presentation
- Genotypically male but female external genitalia.
- No male or female internal genitalia
- Has testis within abdominal cavity
Why do AIS patients have no male or female internal genitalia?
- Y chromosome
- SRY proteins expressed
- gonad –> testis
- sertoli cells from primitive sex cords
- AMH degenerates mullerian ducts so NO internal female genitalia
- leydig cells produce testosterone but undetected so Wolffian duct regresses
Why do AIS patients have a female external genitalia?
- 5-a-reductase in genital skin convert testosterone into DHT
- DHT also binds to testosterone receptors
- no response
- no external male genitalia
Diagnosis of AIS
- Amenorrhoea
- High levels of testosterone
- Lack of hair
- Ultrasound will show testis within the body
- Karyotyping - Will show XY rather than XX
5-a-reductase deficiency
Testosterone made, acts on body but lack 5-a-reductase SO NO DHT produced
What happens in 5-a-reductase deficiency?
- Y chromosome so SRY
- Forms Testis, sertoli cells, Leydig cells
- Testis + leydig cells form testosterone
- Forms internal male genitalia from Wollfian ducts.
- Sertoli cells produce AMH degenerating Mullerian ducts so female internal genitalia not made
- Testosterone wants to get converted into DHT via 5-a-reductase BUT lack so lack development of male external genitalia.
why does 5-a-reductase deficiency differ?
Some people may continue to develop male external genitalia once puberty as HIGH testosterone so HIGH substrate which may tip the development to correct side (more substrate = more product even if the reaction is slower due to a decreased amount in the enzyme)
Presentation of Turner’s
- no Y chromosome
- no SRY
- produce Ovaries
- no AMH so Mullerian ducts continue growing
- Testosterone levels wouldn’t be high so Wollfian ducts regress.
- internal + external female genitalia.
Complications in turner syndrome patients
- Failed ovarian function - due to only 1 X chromosome
- Streak ovaries - ovarian dysgenesis (both chromosomes required for normal development of ovaries)
- Uterus + uterine tubes - small but present
- Growth + puberty problems
- Infertility (mocaicisim - increases the chances of fertility)
treatment Turner’s
Hormone support - for bones and the uterus
CAH (Congenital Adrenal Hyperplasia) cause?
No cortisol production due to lack of 21-hydroxylase.
CAH (Congenital Adrenal Hyperplasia) problem of HPA axis
- lack of 21-hydroxylase
- no cortisol
- no negative feedback inhibiting continuous production of CRH +ACTH
- build up of androgens in adrenal cortex as desired cortisol/aldosterone not be produced.
Presentation CAH
- XX no SRY
- Gonads –> ovaries
- Lack sertoli cells = no AMH so mullerian cells develops female internal genitalia
- Lack leydig cells = no testosterone from them via defective 21-hydroxylase BUT rather than cortisol being produced, androgens including testosterone is produced.
- testosterone –> internal male genitalia from Wollfian ducts.
- Testosterone –> DHT –> external male genitalia even if genotype XX
Complications of CAH
- various degree of enzyme block which is specific to each individual patient
- No aldosterone so lethal salt wasting
CAH treatment
Treated with glucocorticoids (cortisol) to correct feedback.
Exogenous cortisol return negative feedback + present salt wasting.
AIS genotype + internal/external genitalia
XY
internal = female
external = female
5-a-reductase deficiency genotype + internal/external genitalia
XY
internal = make
external = female
Turner’s genotype + internal/external genitalia
XO
internal = female
external = female
CAH genotype + internal/external genitalia
XX
internal = male + female
external = male
How does oestrogen and oestradiol differ?
Oestradiol has varying numbers of -OH groups
Why does the adrenal cortex produce sex hormones?
All the cholesterol-based hormones are made in a chain reaction to produce cortisol + aldosterone, adrenal cortex first produces sex hormones.
21-hydroxylase
form aldosterone + cortisol
Hypothalamic-pituitary-adrenal axis
- hyprothalamus releases CRH (corticotropin releasing hormone)
- stimulates cells in A.pituitary
- release ACTH (adrenocorticotropic hormones)
- work on adrenal cortex to produce cortisol.
- system runs on negative feedback.
ACTH
- Increasing uptake of cholesterol in adrenal cortex
- Upregulating expression of the cholesterol cleaving enzymes - p450 enzymes
- secretion of glucocorticoids decrease.
