Sexual Differentiation Flashcards
determinants of biologic sex
- chromosomes
- gonads
- hormones
- internal genitalia
- external genitalia
bipotential gonads
*in utero, we have bipotential gonads (could become ovaries or testicles)
*chromosomes help them “make that decision”
*default pathway = ovaries
sex determination - female
- chromosomes: XX
- gonads: bipotential gonads remain on “default pathway” → ovaries in the absence of “other factors” (e.g. absence of SRY gene from Y chromosome)
- hormones: granulosa cells of ovaries → estradiol
- internal genitalia: default biology → preservation of Mullerian structures → development of uterus, fallopian tubes, upper vagina
- external genitalia: default = female
sex determination - male
- chromosomes: XY
- gonads: bipotential gonads deviate from the default pathway, initiated by SRY region of Y chromosome → TDF → testicles
- hormones: Leydig cells of testes → testosterone
- internal genitalia: anti-mullerian hormone & testosterone → involution of Mullerian structure & preservation of Wolffian structure → development of male internal genitalia
- external genitalia: requires DHT to drive process to development of male external genitalia
effects of Y chromosome on gonadal differentiation into testes
*default pathway of gonads is to become ovaries
*the presence of a specific region on the Y chromosome induces deviation from the default pathway and therefore development of testes
*SRY gene (sex-determining region of the Y chromosome) → production of TDF (testis-determining factor) → formation of testicles
what enzyme converts testosterone to estradiol
*AROMATASE is the enzyme that converts testosterone into estradiol
what does the Wolffian duct become
*seminal vesicles
*epididymis
*ejaculatory duct
*vas deferens
what does the Mullerian duct become
*uterus
*fallopian tubes
*upper vagina
default internal genitalia pathway
*default biology = biologically female
*INVOLUTION of Wolffian structures
*PRESERVATION of Mullerian structures → development of uterus, fallopian tubes, & upper vagina
*note - nothing “causes” this to happen
development of male internal genitalia
*requires factors in order to deviate from default (female) pathway to the male pathway
*INVOLUTION of Mullerian structures; factor responsible = anti-mullerian hormone
*PRESERVATION of Wolffian structures; factor = testosterone → development of seminal vesicles, epididymis, ejaculatory duct, vas deferens
what factor is responsible for inducing involution of Mullerian structures in biological males
*Anti-Mullerian Hormone
*produced by Sertoli cells in the testes
what factor is responsible for inducing preservation of Wolffian structures in biological males
*testosterone
*produced by Leydig cells in the testes
what hormone is responsible for inducing development of male external genitalia
*DHT (dihydrotestosterone)
3 rules of sexual differentiation
- natural, unperturbed state is typically FEMALE (ovary-Mullerian-external female)
- the Y chromosome (SRY gene) produces the testes, which produces testosterone (assuming that SRY gene is intact)
- testosterone & dihydrotestosterone produce “male anatomy” (assuming that the androgen receptors work)
Klinefelter Syndrome - overview
*47, XXY
*hyalinization of seminiferous tubules & aggregation of Leydig cells
*typically manifests in adolescence
*remains a phenotypic male
Klinefelter Syndrome - clinical features
*small, atrophied testes (“hyalinized”)
*low testosterone & azoospermia/infertility
*gynecomastia
*increased risk of breast cancer
*decreased facial & axillary hair
*decreased libido
*tall stature, increased leg length
pathogenesis of gynecomastia in Klinefelter Syndrome
*poor production of testosterone → pituitary revs up production of FSH & LH to attempt to compensate → LH stimulates aromatase which converts testosterone to estrogen
*increased estrogen → gynecomastia and increased risk of breast cancer
Turner Syndrome - overview
*45X
*short stature & pubertal delay = Turner Syndrome until proven otherwise
*ovaries do not fully develop (“streak gonads”), but default female process otherwise proceeds
*dx = karyotype
Turner Syndrome - clinical features
*infancy: lymphedema, webbed neck, shield-shaped chest, cardiac defects (bicuspid aorta & coarctation), horseshoe kidney
*childhood: short stature, cubitus valgus, sensorineural hearing loss, ptosis, amblyopia
*adulthood: pubertal failure & primary amenorrhea, autoimmune thyroid disease, osteoporosis, hearing loss
note - do not have to have many/all of these features; short stature & pubertal delay = Turner Syndrome until proven otherwise
46, XY complete gonadal dysgenesis
*Y chromosome has mutation or deletion of SRY gene, resulting in default female sexual development
*female phenotype with streak gonads
*risk of gonadal neoplasms
*treatment: estrogen replacement, gonadal removal due to risk of gonadoblastoma in dysgenic gonads
androgen insensitivity syndrome
*karyotype XY
*testosterone and LH are high
*no androgen effect noted (due to ineffective testosterone receptors so no effects from testosterone)
*male gonadal sex (testicles & hormones) but female EXTERNAL genitalia
*therapy: estrogen replacement
genetic female [XX] with male phenotypic features due to congenital adrenal hyperplasia
*enzyme deficiency, commonly in 21-hydroxylase, leading to inability to produce cortisol
*leads to buildup of precursor 17-alpha hydroxyprogesterone
*excess testosterone production by the adrenal glands
*can have normal sexual function, including fertility (only the external genitalia are affected; internal genitalia differentiate at 10 weeks gestation, but adrenal gland does not function until 12 weeks)
*represents the only life-threatening disorder of sexual differentiation
*abnormalities may vary from slight clitoromegaly to full-fledged male appearance (with apparent cryptorchidism)
genetic female [XX] with male phenotypic features due to maternal androgen excess
*excess maternal androgens, either from:
-exogenous androgens OR
-ovarian or adrenal tumors
5-alpha reductase deficiency
*5-alpha reductase is the enzyme that converts testosterone to dihydrotestosterone (DHT)
*DHT is important for growth and development of the penis & prostate
*results in genetic male [XY] with:
-pre puberty: FEMALE external genitalia
-post puberty: MALE external genitalia
