Intro to Reproduction and Sexual Differentiation Flashcards
What is the difference between sexual determination and sexual differentiation?
Sexual determination is the genetically controlled process dependent on the ‘switch’ on the Y chromosome - chromosomal determination of male or female.
Sexual differentiation is the process by which internal and external genitalia develop as male or female.
What are the different ‘levels’ of sex differentiation?
- genotypic sex
- gonadal sex
- phenotypic sex
- legal sex
- gender identity
After fertilisation a pair of gonads develop which are bi-potential (neither testis or ovaries). What determines differentiation of the bi-potential gonad into a testis or an ovary?
Depends upon the sperm that fertilises the oocyte…
- Y sperm -> testes
- X sperm -> ovary
Which gene creates the testis?
SRY gene (on short arm of Y chromosome) - after week 7 it switches on to make the gonad into a testis.
In absence of Y ovaries would develop.
What cells does the testis develop and what 2 important hormones do they make?
- Sertoli cells: produce anti-Mullerian hormone (AMH)
- Leydig cells: make testosterone
What is the precursor of bipotential gonads that are produced following fertilisation?
Common somatic mesenchymal tissue precursors termed ‘genital ridge primordia’ on posterior wall of lower thoracic lumbar region.
What two ducts do bipotential gonads contain?
- Mullerian - for females, develop into internal female genitalia (uterus, upper 3rd vagina + uterine tubes)
- Wolffian - for males, develop into internal male genitalia (seminal vesicles, vas deferens, prostate)
Describe primordial germ cell migration and what they become
They present as a small cluster of cells in the epithelium of the yolk sac, expanding by mitosis (~3 weeks). They then migrate to connective tissue of hindgut to region of developing kidney + on to genital ridge (by 6 weeks).
In males, PGCs -> spermatozoa
In females, PGCs -> oocytes
What are Primitive Sex Cords and how do they develop?
Cells from germinal epithelium that overly the genital ridge mesenchyme migrate inwards as columns called primitive sex cords.
They depend on SRY expression.
- M: SRY expression -> testis cords -> sertoli cells -> AMH
- F: No SRY expression -> granulosa cells -> estradiol
Where do Mesonephric Cells originate from?
The mesonephric primordium which are just lateral to the genital ridges
When and what do mesonephric cells differentiate into?
Depend on SRY once again
- MALES: pre-sertoli cells (SRY) -> vascular tissue + Leydig cells + basement membrane (contrib to formation of seminiferous tubules + rete-testis)
- FEMALES: without SRY -> vascular tissue + theca cells
What do Theca cells produce?
Synthesize androstenedione, which is a substrate for estradiol production by the granulosa
What does AMH do?
Inhibits mullerian ducts (which are important in female) - so will be present in males.
What does testosterone do?
Stimulates wolffian ducts - lack of stimulation by testosterone means regression of Wolffians (such as in females)
Where is 5-a-reductase found?
Found in the skin of a penis in a male or genital skin.
What does 5-a-reductase produce?
Produces a more potent androgen - DHT (dihydrotestosterone) from testosterone.
How does DHT bring about differentiation?
It can also bind to testosterone receptors but is more potent.
Causes differentiation of the male external genitalia:
- Clitoral area enlarges into penis
- Labia fuse + become ruggated to form scrotum
- Prostate forms
Describe female internal sexual differentiation
- No Y chromosome -> no SRY -> no testis -> no AMH
- Ovary develops (XX)
- (No AMH ->) Mullerian ducts form: uterine tubes, uterus and upper 3rd vagina
- > Upper ends of ducts stay open and form ends of uterine tubes
- > Lower portions fuse to form a single cavity uterus
What happens in terms of sexual differentiation in the absence of DHT?
The female external genitalia form instead; clitoria, labia and lower 2/3rds of vagina.
What is gonadal dysgenesis?
Sexual differentiation is incomplete due to partial or complete regression of the gonad - AIS, intersex and CAH, all cause gonadal dysgenesis, with individuals having ambiguous genitalia.
What is sex reversal?
When the phenotype does not match the genotype ie. may be male genotypically but externally look like a female
What is intersex?
Have some components of both tracts or have ambiguous genitalia. Sex of infant is difficult to determine.
What is Androgen Insensitivity Syndrome (AIS)?
The testes are able to form due to presence of SRY. Make AMH so Mullerian (female duct) regresses. Testosterone is made but it cannot exert an effect due to the absence of receptors. The Wolffian tract/internal male genitalia and external male genitalia (via DHT) therefore do not develop and so the phenotype is female. These individuals present with primary amenorrhoea
What is the difference between partial and complete Androgen Insensitivity Syndrome (AIS)?
- Complete - appear completely female at birth and assigned female gender despite being XY, have undescended testes. Present with primary amenorrhoea + lack of body hair. Appear and feel female.
- Partial - some penile/scrotal development from ambiguous genitalia to large clitoris. Much more complex for parents and patient.
