BIOL 3010 Lecture Notes - Androgen Insensitivity Syndrome, Dihydrotestosterone, Aromatase

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29 Jan 2013
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Reproductive System
Integrated with urinary system development
relies upon mesonephric ducts (Wolffian ducts)
form vas deferens and epididymis in males
closed system
Mullerian ducts - paramesonephric ducts that arise alongside
mesonephric ducts
derived from surface epithelium
form oviducts/uterus of female
**Embryos are IDENTICAL until week 6 after this, genetic sex is
expressed**
PRIMORDIAL GERM CELLS –
arise very early in development, distinct from gonad position
- endodermal, highly motile (large filopodia)
- proliferate as they migrate to the gonadal ridge
Migration:
- c-Kit receptor (migration along genital ridge)
- B-1 integrin
- SDF-1/ CXCR4 (migration into genital ridge)
Survival/Proliferation:
- SCF/c-KIT (survival)
- Pin-1 (increase cell cycle rate inc. proliferation)
- SDF/CXCR4 (survival)
PGC’s are not required for testes, but ARE required for ovaries
GERM CELL FATES
XY PGC’s in testes will have MITOTIC arrest until puberty
XX PGC’s in testes will die after mitosis resumes at puberty
XY PGC’s in ovaries will have MEOTIC arrest until puberty
**XY PGC’s in ovaries may survive after meosis resumes**
Wolffian
Mullerian
PGC
c-kit
B-1 integrin
SDF-1/CXCR4
SCF
Pin-1
mitotic arrest
meiotic arrest
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Reproductive System
CENTRAL DOGMA OF SEX DEVELOPMENT
genetic sex gonadal sex phenotypic sex
(no gonads phenotypically female)
Genetic Sex determination:
depends on Y chromosome
locus of sry gene codes for TDF (TF)
(testes-determining factor)
downstream targets of TDF not yet id’d
sry expression is necessary but not sufficient for:
testis development (not ovaries)
sperm (not oocytes)
sertoli cells (not follicle granulosa cells)
leydig cells (not theca cells)
peritubular tunica (not stromal tunica)
other important genes –
Sox9 – mutations cause XY females
DaxI, Wnt4 – duplications cause XY females
Phenotypic Sex: (Genital ducts determined by gonads present)
testis present Wolffian ducts remain (testosterone effect)
Mullerian ducts regress (MIS effect)
grafting experiments:
remove testes early only Mullerian ducts are present
late both sets present and incomplete
(more Mullerian than Wolffian)
add testes unilaterally same side Wolffian present
opposite side ½ present
(testosterone operates over small distances only)
same side Mullerian gone
opposite side FULLY present
(MIF operates over small dist. also)
add testosterone bead Wolffian present
Mullerian also present
sry, TDF
Sox9
DaxI, Wnt4
testosterone
MIS (Mullerian
inhibiting substance)
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