Lecture 1+2 Flashcards
Pairs of similarly sized chromosomes:
Females have 8, including the 2X.
Males have 7.5, because Y is smaller.
Reasons that genetic identity is maintained in mitosis:
Homologous chromosomes don’t exchange genetic material - sister chromatids are identical.
Meiosis events:
Meiosis I: recombination and reduction to haploid. homologues split.
Meiosis II: chromatids separate.
Spermatogenesis:
Spermatogonium (2N) -- duplication -- Primary spermatocyte (4N) -- telophase I -- 2 secondary spermatocytes (2N) -- after meiosis II -- 4 spermatids (1N) -- after maturation -- 4 spermatozoa (1N)
Oogenesis:
Oogonium (2N) -- duplication -- Primary oocyte (4N) -- prophase I -- Arrested primary oocyte (4N) -- meiosis I -- Secondary oocyte (2N) and polar body #1 -- separation of chromatids -- Mature oocyte (1N) and polar body #2
Sex determination: genetic sex
Determined at fertilization: whether sperm bears X or Y.
Sex determination: genotypic sex
Determined by parental sex chromosomes.
Sex determination: gonadal sex
Determined by genotypic sex at 9 weeks of gestation.
External genitalia is expressed after gestation, 38-40 weeks.
Sex determination: phenotypic sex
Determined by gonadal sex at puberty.
Epigenetics:
A change in phenotype without a change in genotype.
Probably happen due to DNA methylation and histone modification.
In fetuses, epigenomes direct stem cell differentiation.
Development of testes:
Cortex regresses into tunica albuginea. Medulla develops. Primary sex cords hollow out to become seminiferous tubules.
Development of ovaries:
Cortex becomes more pronounced and more vascularized at the expense of the medulla.
Default sex:
Female. Need lots of conditions to make male.
Testis-determining effect of Y chromosome:
Male sex is established when Y tells primary sex cords to differentiate into seminiferous tubules.
TDF/SRY:
A single gene located on the short arm of the Y chromosome. Needed for testicular development.
Translocation of TDF:
XX male. During father’s meiosis, X and Y chromosomes recombine at distal end of short arms.
Sterile with small testes and feminine traits.
Gonadal dysgenesis: XO
Loss of one X chromosome. Gonads appear as a streak or line in the adult pelvic sidewall.
Gonadal dysgenesis: Turner syndrome
Most common example of gonadal dysgenesis.
45 XO. Females with short stature, primary amenorrhea, sexual infantalism.
SRY-related abnormalities: 46 XX
True hermaphrodites. No Y chromosome but still have testes - possess both male and female sex organs.
SRY-related abnormalities: 45 XO
Pseudohermaphrodites - only one type of gonadal tissue, but morphological characteristics of both sexes. Testes and ovary streak.
Male development of genital ducts:
Paramesonephric/Mullerian duct degenerates. Mesonephric/Wolffian duct develops into vas deferens, seminiferous tubules, ejaculatory duct.
Female development of genital ducts:
Mesonephric/Wolffian duct degenerates. Paramesonephric/Mullerian duct develops into oviduct, uterus, and upper third of vagina.
Removing both testes:
Stops production of testosterone and anti-Mullerian hormone. Mullerian ducts will develop and Wolffian ducts will degenerate. Chromosomal male but phenotypic female.
Removing ovaries:
Mullerian development continues as normal. Ovaries aren’t necessary for female duct development.
Removing one testis before puberty:
Ipsilateral development of mullerian duct. Other side develops normally - virilization of external genitalia occurs as normal.
Removing both testes and administering testosterone:
Wolffian ducts develop normally. Mullerian ducts do not regress in the absence of AMH.
Treating a female with testosterone:
Promote development of Wolffian ducts. Mullerian ducts develop normally in absence of AMH.
Hormones necessary for male differentiation:
Testosterone (testes)
AMH (testes)
Dihydrotestosterone (peripheral tissues)
Enzyme that converts testosterone to DHT?
5-alpha-reductase
When does testicular development occur?
Before 9 weeks of gestation, in the presence of TDF. If TDF is not present during the critical window, ovaries will develop.
Two major roles of androgens in male phenotypic differentiation:
Trigger conversion of W ducts to ejaculatory system. Direct differentiation of urogenital sinus and external genitalia.
Wolffian phase regulated by which hormones?
Testosterone only. Doesn’t care about DHT.
DHT is required for:
Virilization of urogenital sinus, prostate, penile urethra, and external genitalia during embryogenesis.
Sexual maturation at puberty.
After formation of testicular cords…
Sertoli cells produce AMH. Leydig cells produce testosterone. If embryo doesn’t get enough androgens or doesn’t have enough androgen receptors, sexual ambiguity occurs.
Sertoli cells produce:
AMH for obvious reasons.
ABP to maintain a high local concentration of testosterone, for development of W ducts/medulla/prostate.
First site of androgen action:
Embryonic mesenchyme has androgen receptors.
Do W ducts require DHT?
Nope. They don’t have 5-alpha-reductase, so they have to make do with reg ole (T).
Is DHT required for development of external genitalia?
Yup. Absence of 5-alpha-reductase results in normal development of W duct but impaired virilization of external genitalia.
W ducts develop into:
Medulla develops into:
Epididymis, vas deferens, seminal vesicles, ejaculatory duct.
Rete testis.
Where are male steroids produced? Where are female steroids produced?
Male: testes, because they produce 1000x more than adrenal glands.
Female: adrenal glands.
Cortisol:
Stress response.
Fights infection - hydrocortisol mimics body’s nature response to infection.
Aldosterone:
Controls salt/water level in blood, regulates salt/water excretion.
Effect of too much aldosterone:
Too much aldosterone -> too much salt -> more water retention -> increased blood pressure.
Congenital adrenal hyperplasia:
Deficiency in 3-beta, 21-alpha, or 11-beta enzymes. Results in virilization of females. Ambiguous genitals due to hypersecretion of androgens.
Most common congenital adrenal hyperplasia:
21-alpha deficiency - 95% of cases. Blocks both aldosterone and cortisol pathways, so adrenal steroid precursors are shunted to androgen pathways.
Adrenogenital syndrome:
Too much androgen! Enlarged clitoris, fused/enlarged labioscrotal folds. Otherwise normal female infant.
Androgens in feminization syndrome:
Testicular descent is dependent on androgens. 5-alpha-reductase deficiency and androgen resistance - testes fail to descend.
Androgens in male pseudohermaphroditism:
Defect in androgen action mechanisms. Unambiguous male gonads but ambiguous genitalia or phenotypically female.
5-alpha-reductase deficiency:
Autosomal recessive; only expressed in males. Lack of DHT leads to ambiguous genitalia, blind vaginal pouch, bound/hooded phallus, hypospadias (pee hole too low).
DHT vs (T):
DHT binds same receptor but with 100x stronger affinity.
DHT-receptor complex binds chromatin more tightly than the (T)-receptor complex.
Androgen receptor:
Present in genital tissues.
Homodimer - a member of nuclear receptor family.
AR/AR receptor complex:
Transcription factor for hormone response elements on androgen-controlled genes. Increases transcription by interaction between receptor-steroid complex and chromatin.
Absent or abnormal androgen receptors lead to:
Testicular feminization
Inadequate androgen production or nonfunctioning androgen receptors lead to:
Sexual ambiguity
AMH: structure
Homodimer of two monomeric glycoprotein subunits linked by disulfide bond.
Mechanism of action of steroid hormones:
Diffuse into cell.
- Bind to receptor in cytosol. Diffuse into nucleus. Affect transcription.
- Bind to receptor in nucleus. Affect transcription.
