Mammalian sex determination, development 2

Question 1

migration of primordial germ cells

Answer 1

• 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

Question 2

what are all germ cells potentially

Answer 2

female (irrespective of genetic sex) unless they migrate to a developing testis and are enclosed in the seminiferous cords

Question 3

what happens when germ cells enter seminiferous cords

Answer 3

both XX and XY germ cells will enter mitotic arrest and develop as t-spermatogonia

Question 4

what is the fate of germ cells to continue mitosis (testis) or meiosis (ovary) determined by

Answer 4

exposure to either Fgf9 (prevents entry into meiosis) or retinoic acid (promotes it)

Question 5

what does differentiation into oocytes or spermatogonia depend on

Answer 5

the gonadal environment in which they find themselves, not their genetic makeup

Question 6

what does the presence of only one X chromosome do in oogonia

Answer 6

causes a reduction in ocoyte survival during meiosis

Question 7

what does the presence of XX in germ cells of the testicle result in

Answer 7

infertility

Question 8

what does differentiation of the bipotential gonad determine

Answer 8

its major hormonal products –> determines further sexual differentiation

Question 9

what do functional testes secrete

Answer 9

• testosterone
• anti-mullerian hormone (AMH)/mullerian-inhibiting substance (MIS)
• insulin-like factor 3 (INSL3)

Question 10

what is estrogen vital for

Answer 10

• changes seen during and after puberty

- no role in development of the ovary or female phenotype during fetal life

Question 11

once a testicle has been formed, the remainder of mammalian sexual differentiation is due to what

Answer 11

hormonal products (testosterone, MIS, INSL3) –> drive genetic cascades to give male phenotype (castration before testis determination results in phenotypically female animal)

Question 12

where are androgens produced

Answer 12

from cholesterol in the leydig cells of the testicle

Question 13

2 androgens

Answer 13

• testosterone (major androgen produced)

- dihydrotestosterone (formed from testosterone by 5alpha-reductase enzyme)

Question 14

3 stages of testosterone secretion

Answer 14

1. during gestation (masculinize fetal genetalia)
2. perinatal (sets brain sex)
3. puberty (secondary sex characteristics, spermatogenesis)

Question 15

mullerian inhibiting substance

Answer 15

• glycoprotein produced by sertoli cells
• causes regression of mullerian ducts in males
• male specific until after birth (high levels)

Question 16

when do rudimentary female ducts develop

Answer 16

after the early indifferent gonad is visible

Question 17

names of male and female ducts

Answer 17

• male: mesonephric or wolffian

- female: paramesonephric or mullerian

Question 18

what do efferent ducts do and where do they arise from

Answer 18

• connect the rete testes to the epididymus

- arise from residual mesonephric tubules

Question 19

what happens to urogenital folds in males

Answer 19

elongate and fuse to form penile shaft

Question 20

what happens to genital swellings in males

Answer 20

fuse to form the scrotum

Question 21

what happens to the genital tublercle in males

Answer 21

develops into glans penis

Question 22

what are positive effects of reproductive tract male sex differentiation controlled by

Answer 22

androgens

Question 23

what are negative aspects of male differentiation controlled by

Answer 23

MIS (AMH)

Question 24

testosterone and androgen receptor

Answer 24

• signals differentiation of the wolffian duct in male embryo
• regulates hypothalamo-pituitary axis for LH secretion
• vital role in spermatogenesis

Question 25

dihydrotestosterone and androgen receptor

Answer 25

- signals development of external genitalia and prostate - elongation and ventral closure of the penile anlagen - pubertal changes, baldness, external genitalia maturation, male behavior

Question 26

what causes different effects of T and DHT when they have the same receptor

Answer 26

- 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)

Question 27

what does MIS/AMH do

Answer 27

causes regression of the mullerian ducts in male fetuses --> acts locally by diffusion

Question 28

what occurs first - regression of mullerian duct in males or regression of wolffian duct in females

Answer 28

regression of mullerian duct in males

Question 29

when are mullerian ducts of developing embryos sensitive to MIS

Answer 29

for a limited period of time shortly after gonadal sex differentiation

Question 30

what happens to the ducts in the absence of testosterone

Answer 30

wolffian ducts in female fetuses regresses while mullerian ducts develop in the absence of MIS

Question 31

where do the oviducts develop from

Answer 31

the cranial portion of the mullerian duct adjacent to the ovary

Question 32

when do the fimbria develop

Answer 32

after the rest of the oviduct (may be after birth)

Question 33

uterine and cervical development

Answer 33

fusion of the left and right mullerian ducts to varying degrees

Question 34

do females have angrogen receptors and/or 5alpha-reductase enzyme present

Answer 34

yes --> could be masculinized if exposed to androgens

Question 35

steps in X inactivation

Answer 35

1. x chromosomes counted 2. choose which to inactivate 3. developmental cue triggers inactivation at the x-inactivation center (xic) 4. inactivation spreads 5. inactivation is stabilized and clonally transmitted

Question 36

what cells does x-inactivation involve

Answer 36

all somatic cells of the female embryo

Question 37

model for x-inactivation

Answer 37

- 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

Question 38

do all parts of affected chromosome undergo inactivation

Answer 38

no --> some parts escape it (especially in homologous genes - PAR)

Question 39

2 stages of testicular descent (biphasic model)

Answer 39

- transabdominal descent | - inguino-scrotal descent

Question 40

overview of transabdominal testicular descent

Answer 40

- testicles go from abdomen to internal inguinal ring | - gubernaculum thickens, testicle anchored to internal inguinal region

Question 41

what happens to gubernaculum in females

Answer 41

- regresses to a long, thin band of tissue | - female gonad relatively tightly bound to the dorsal body wall

Question 42

what hormone is responsible for gubernacular growth

Answer 42

insulin-like factor 3 from leydig cells --> GREAT receptor

Question 43

what is another name for the gubernaculum

Answer 43

caudal suspensory ligament

Question 44

overview of inguinoscrotal desent

Answer 44

- testicles go through inguinal canal to scrotum | - gubernaculum regresses, pulls epididymis and testicle into scrotum

Question 45

what forms from the outer ring of the gubernaculum

Answer 45

cremaster muscle

Question 46

what is inguinoscrotal movement of the gubernaculum controlled by

Answer 46

angrogens, acts via genitofemoral nerve

Question 47

what does the genitofemoral nerve do under the influence of androgens

Answer 47

releases the neurotransmitter calcitonin gene-related peptide (CGRP)

Question 48

what does CGRP do

Answer 48

causes growth of the tip of the gubernaculum and directs its migration through the inguinal canal and into the scrotum

Question 49

causes of cryptorchidism

Answer 49

- defect in the androgen pathway for inguinoscrotal descent - defect in prenatal androgen secretion - mechanical, neurological problems

Question 50

problems with cryptorchidism (3)

Answer 50

- infertility - tumor formation (sertoli cell tumor, seminoma) - heritability (autosomal recessive)