5-350 Lecture Notes - Lecture 19: Klinefelter Syndrome, Sertoli Cell, Dihydrotestosterone

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Published on 28 Jan 2013
Course
Outline of Lecture 19
Sex Determination and Differentiation
I. Embryologic origin of the reproductive system
- At 4th week, intermediate mesoderm gives rise to mesonephros; the mesonephric
(Wolffian) ducts give rise to epididymis and vas deferens in male
- At 6th week, intermediate mesoderm give rise to paramesonephric (Müllerian)
ducts, which give rise to oviducts and uterus in female
- Hox genes are involved in A/P patterning of urogenital tract
- Primordial germ cells
- Arise in primitive streak and endoderm, migrate to yolk sac, then back to
genital ridge
- Migration requires Steel factor
- In females, number of germ cells spikes the quickly falls in fetus, and
experiences steady decline throughout life; in males, number of germ cells
are constantly renewed
- Can be used as a source of embryonic stem cells
- Fate of PGC (male G1 arrest, female prophase I arrest) in embryo is determined
by environment, but postnatal fate depends on genetic makeup
II. Control of sexual development
A) It is a sequential process: genetic sex gonadal sex phenotypic sex
B) Gonad, urogenital sinus, external genitalia, etc. develop from bipotential
precursors
C) Default pathway is female; SRY is the testis-determining factor
- Testis development requires SRY, a txn factor coded by the Y
chromosome
- Other factors besides SRY also determine sex
- Wt-1 and SF-1 needed for gonad development
- SOX9 has similar role to SRY
- Dax1 and Wnt4a has role in ovary development
D) Both duct systems develop, then one regresses in normal development
- Female sex differentiation is independent of gonadal hormones and
ovaries
- MIS (member of TGF-β) is secreted by the Sertoli cells of the testes, and its
expr during a critical period of responsiveness causes regression of
Müllerian ducts
- Testosterone is a steroid hormone produced by the Leydig cells of the testes, and
is needed for Wolffian duct structures
- The enzyme 5α-reductase converts T to dihydrotestosterone; DHT promotes
mascularization of urogenital sinus mesenchyme and development of
external genitalia
- Urogenital sinus mesenchyme delivers instructive induction signals to
u.s. epithelium
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