Mammalian sex determination, development 2 Flashcards
migration of primordial germ cells
- sometimes migrate to extragonadal sites (adrenals or kidneys)
- all of them differentiate as oocytes and enter meiosis at the same stage as oocytes
- later degenerate
what are all germ cells potentially
female (irrespective of genetic sex) unless they migrate to a developing testis and are enclosed in the seminiferous cords
what happens when germ cells enter seminiferous cords
both XX and XY germ cells will enter mitotic arrest and develop as t-spermatogonia
what is the fate of germ cells to continue mitosis (testis) or meiosis (ovary) determined by
exposure to either Fgf9 (prevents entry into meiosis) or retinoic acid (promotes it)
what does differentiation into oocytes or spermatogonia depend on
the gonadal environment in which they find themselves, not their genetic makeup
what does the presence of only one X chromosome do in oogonia
causes a reduction in ocoyte survival during meiosis
what does the presence of XX in germ cells of the testicle result in
infertility
what does differentiation of the bipotential gonad determine
its major hormonal products –> determines further sexual differentiation
what do functional testes secrete
- testosterone
- anti-mullerian hormone (AMH)/mullerian-inhibiting substance (MIS)
- insulin-like factor 3 (INSL3)
what is estrogen vital for
- changes seen during and after puberty
- no role in development of the ovary or female phenotype during fetal life
once a testicle has been formed, the remainder of mammalian sexual differentiation is due to what
hormonal products (testosterone, MIS, INSL3) –> drive genetic cascades to give male phenotype (castration before testis determination results in phenotypically female animal)
where are androgens produced
from cholesterol in the leydig cells of the testicle
2 androgens
- testosterone (major androgen produced)
- dihydrotestosterone (formed from testosterone by 5alpha-reductase enzyme)
3 stages of testosterone secretion
- during gestation (masculinize fetal genetalia)
- perinatal (sets brain sex)
- puberty (secondary sex characteristics, spermatogenesis)
mullerian inhibiting substance
- glycoprotein produced by sertoli cells
- causes regression of mullerian ducts in males
- male specific until after birth (high levels)
when do rudimentary female ducts develop
after the early indifferent gonad is visible
names of male and female ducts
- male: mesonephric or wolffian
- female: paramesonephric or mullerian
what do efferent ducts do and where do they arise from
- connect the rete testes to the epididymus
- arise from residual mesonephric tubules
what happens to urogenital folds in males
elongate and fuse to form penile shaft
what happens to genital swellings in males
fuse to form the scrotum
what happens to the genital tublercle in males
develops into glans penis
what are positive effects of reproductive tract male sex differentiation controlled by
androgens
what are negative aspects of male differentiation controlled by
MIS (AMH)
testosterone and androgen receptor
- signals differentiation of the wolffian duct in male embryo
- regulates hypothalamo-pituitary axis for LH secretion
- vital role in spermatogenesis
dihydrotestosterone and androgen receptor
- signals development of external genitalia and prostate
- elongation and ventral closure of the penile anlagen
- pubertal changes, baldness, external genitalia maturation, male behavior
what causes different effects of T and DHT when they have the same receptor
- differences in binding affinity (DHT has higher affinity for AR (androgen receptor) than T)
- effect on receptor function (DHT-AR activates some genes more easily than T-AR)
what does MIS/AMH do
causes regression of the mullerian ducts in male fetuses –> acts locally by diffusion
what occurs first - regression of mullerian duct in males or regression of wolffian duct in females
regression of mullerian duct in males
when are mullerian ducts of developing embryos sensitive to MIS
for a limited period of time shortly after gonadal sex differentiation
what happens to the ducts in the absence of testosterone
wolffian ducts in female fetuses regresses while mullerian ducts develop in the absence of MIS
where do the oviducts develop from
the cranial portion of the mullerian duct adjacent to the ovary
when do the fimbria develop
after the rest of the oviduct (may be after birth)
uterine and cervical development
fusion of the left and right mullerian ducts to varying degrees
do females have angrogen receptors and/or 5alpha-reductase enzyme present
yes –> could be masculinized if exposed to androgens
steps in X inactivation
- x chromosomes counted
- choose which to inactivate
- developmental cue triggers inactivation at the x-inactivation center (xic)
- inactivation spreads
- inactivation is stabilized and clonally transmitted
what cells does x-inactivation involve
all somatic cells of the female embryo
model for x-inactivation
- Xp inactivated in all cells before differentiation
- early blastocyst: Xp re-activated in cells of inner cell mass (ICM)
- cells of ICM undergo random x-inactivation
do all parts of affected chromosome undergo inactivation
no –> some parts escape it (especially in homologous genes - PAR)
2 stages of testicular descent (biphasic model)
- transabdominal descent
- inguino-scrotal descent
overview of transabdominal testicular descent
- testicles go from abdomen to internal inguinal ring
- gubernaculum thickens, testicle anchored to internal inguinal region
what happens to gubernaculum in females
- regresses to a long, thin band of tissue
- female gonad relatively tightly bound to the dorsal body wall
what hormone is responsible for gubernacular growth
insulin-like factor 3 from leydig cells –> GREAT receptor
what is another name for the gubernaculum
caudal suspensory ligament
overview of inguinoscrotal desent
- testicles go through inguinal canal to scrotum
- gubernaculum regresses, pulls epididymis and testicle into scrotum
what forms from the outer ring of the gubernaculum
cremaster muscle
what is inguinoscrotal movement of the gubernaculum controlled by
angrogens, acts via genitofemoral nerve
what does the genitofemoral nerve do under the influence of androgens
releases the neurotransmitter calcitonin gene-related peptide (CGRP)
what does CGRP do
causes growth of the tip of the gubernaculum and directs its migration through the inguinal canal and into the scrotum
causes of cryptorchidism
- defect in the androgen pathway for inguinoscrotal descent
- defect in prenatal androgen secretion
- mechanical, neurological problems
problems with cryptorchidism (3)
- infertility
- tumor formation (sertoli cell tumor, seminoma)
- heritability (autosomal recessive)
