REPRO - Genetics Flashcards
What does SRY transcription factor gene code for? When would it switch on..week.?
male pathway -> testes that make AMH & testosterone
week 7
The bipotential gonads are derived from what?
At week..?
Common somatic mesenchymal tissue “the genital ridge primordia” around week 3/week 4
What is the duct called that forms the: epididymus, vas deferans, prostate gland and seminal vesicles?
Wolffian/mesonephric
What duct forms the uterus, fallopian tubes, cervix and upper 1/3rd of vagina?
Mullerian/paramesonephric duct
What are the 3 waves of cells that invade the genital ridge?
- primordial germ cells (PGCs)
- primitive sex chords
- mesonephric cells
PGCs begin as cell cluster in yolk sac epithelium than expand by mitosis (wk 3) then migrate to….
..CT of the hind gut -> genital ridge (colonised at wk 6)
PGCs form..
- oocytes
- spermatoza
The primitive sex chords are from the germinal epithelium that overlies the genital ridge then migrates.. and in men/women..
inwards as columns
- men: they penetrate the medulary mesenchyme, and surround PGCs forming testis cordis. Become sertoli cells.
- women: ill defined, dont penetrate, condense in cx as clusters around PGCs. Become granulosa cells.
What do sertoli cells express?
AMH (Anti Mullerian Hormone)
Where do mesonephric cells originate?
Mesonephric primordium (lat to genital ridge)
Mesonephric cells in men vs women (make vascular tissue in both)?
Men: pre-sertoli cells and SRY…leydig cells make testosterone, the basement membrane helps to make semineferous tubules and rete testes
Women: Theca cells make adrostenedione, a substrate for E2 production from granulosa.
If men..what about women:
PCG -> spermatoza
P. sex chords -> sertoli cells (AMH, SRY)
mesonephric cells -> Leydig cells (testosterone)
PCG -> oocytes
P. sex chords -> granulosa cells (E2)
mesonephric cells -> Theca cells (androstenedione)
Where is testosterone converted to DHT (dihydrotestosterone) by enzyme…
in the genital skin, by 5a reductase
DHT on the testosterone receptor causes differentiation of ext. male genitalia how?
- genital tubercle and urethral fold enlarges into penis
- genital swellings fuse and become ruggated into scrotum
In females (with no DHT) what does the genital tubercle, swellings and urethral fold form?
- tubercle forms clitoris
- swellings form labia majora and minora
- urethral fold forms opening of vagina
What is testosterone’s function?
-differentiation and growth of Wolffian duct structures (seminal vesicles, vas deferens…)
What leads to the female external genitalia development?
Lack of androgens
What is gonadal dysgenesis? Cause in male/female?
- incomplete sexual differentiation
- missing SRY in males, partial/full deletion of 2nd X in females
what is sex reversal?
When phenotype doesnt match genotype
What is intersex?
When components of both tracts are present or ambiguous genitalia
Androgen Insensitivity Syndrome (AIS) 1/20,000 is due to androgen receptor issue. What happens is..
an XY individual appears female at birth
- they have SRY (make testis, make AMH)
- make testosterone & DHT but no receptors so Wolffian duct cant grow/no ext. male genitalia
How may AIS present?
Primary Amenorrhoea, no body hair, undescended testes..NB they may feel female as brain has been exposed to only female signals
Partial AIS has varying degrees of srotal/penile development, may be large clitoris..ambiguous..ajd at puberty..
..the large androgen surge can cause the appearence of male genitalia on the “female”
5a reductase deficiency is normally A.Recessive condition when testosterone is made but no/little DHT so..
at puberty..
- XY, testis form, AMH, Wolffian ducts grow (int=male)
- no DHT (no ext male so ext=female/ambiguous)
- adrenarche testosterone may induce virilisation so “female” gets male ext genitalia
Turner;s S. (XO) 1/3000, has 1 X due to maternal ovarian dysfunction. No SRY so no AMH, so wolffian regresses and ext=female but you get..
- “streak ovaries”/dysgenesis as we need both X for correct development
- small uterus and tubes and defects in growth and development and infertile (unless mosaic)
No 21-Hydroxylase means no cortisol and lack of neg feedback causes high CRH and ACTH. ACTH at adrenal cx… this is congenital adrenal hyperplasia
..more cholesterol uptake, side chain cleavage by p450s, more glucocorticoid secretions but more androgens as cortisol cant be made
CAH is XX exposed to high androgens in utero, the completeness of the block varies, generally:
XX, no SRY, no testis, no sertoli, no AMH, ovaries form but CAH leads to more testosterone so wolffian and mullerian duct form (both int) and DHT leads to male ext.
Lack of aldosterone in CAH can be lethal by
Whats given to correct feedback in CAH
“salt wasting”
-glucocorticoids
Steroids are made from cholesterol which has:
- # carbons
- # six sided rings
- # 5 sided ring
- with a
- # 24 carbons
- # 3 six sided rings
- # a 5 sided ring
- with a tail
Steroids are made by cutting off carbons of tail/switching groups
- # 21 carbons are
- # 19 carbons are
- # 18 carbons are
21 = progestogens (e.g. progesterone, pregnenolone) 19 = androgens 18 = oestrogens
What is Justice?
Acting in fairness, equal care for all
Ethics. Non-maleficence (avoid unneccessary harm), Benefience (best interests), Justice and what?
Respect Autonomy - enable people to make their own reasoned informed choice
What 3 steps can be taken if you have concerns that a situation is unethical?
- talk to your colleagues
- document your discussions
- contact the ethics committee if needed
