Mammalian sex determination

 1’ sex det  det of the gonads

o primarily chromosomal in nature
o strictly chromosomal in mammals, not usually influenced by environment

 2’ sex det  affects phenotype outside the gonads

o primarily hormonal in nature
o male and female ductal systems and external genitalia
o male: penis, seminal vesicles, prostate gland
o female: vagina, cervix, uterus, oviducts, mammary gland

Sex determination at the chromosome level:

Human sex chromosomes

 +/- of Y chr
 Males: XXY, XXXY
 Rare cases of Primary sex reversal (1:20000 births)
o The X and Y chromosomes [cross over] and exchange genetic material leading to males with two X
chromosomes and females with a Y chromosome

- XX males; XY males with long-arm deletion are still male; XY females but with short arm deletion
- Therefore, “maleness” is determined by something on the short arm of the Y chromosome – SRY.

 Humans usually have 46 chromosomes per diploid cell

o 22 sets of autosomes, 1 set of sex chromosomes (XX or XY)
o usual: karyotype 46, XX  female; 46, XY  male
 How is sex of an individual determined? Number of X chromosomes, or +/- Y chr?
o + Y necessary for male sexual characteristics to develop
o number of X chr does not play a significant role in sex determination

Mammalian Sex Determination

The Jost Paradigm
 typical circumstances, sex of indiv will be determined and expressed thru the ff mechanisms
o chromosomal sex (genetic)  +/- Y chr
o gonadal sex (1’ sex determination)  +/- testis determining factor (TDF)
o phenotypic sex (2’ sex differentiation)  det’d by the hormonal products of gonads

SRY: testis determining gene

 SRY is Y-specific – no analog on X chr
 SRY is deleted or mutated in XY females
 Undergoes expression within the testis at the time of testis differentiation
 Sequence suggests that its protein has a DNA binding motif because it has high homology to an 80aa
long DNA binding region (HMG box)
 i.e., SRY is a member of the HMG group/family of transcription factors (“high mobility group”)

Other Sex determination genes

 Sex differentiation – expression of phenotypic attributes specific to the sex of an individual
 Dax1 – present in bipotential gonad, rapidly downregulated, then confined to female reproductive organ
 Sox9 – present in bipotential gonad, then downregulated at ~11.5dpc in females (not present in female
genitalia)
o Sox9 Induces testis development in XX transgenic mice

Early gonad development

 Metanephros is the functional kidney of the mammals
 Bipotential gonad – bipotential fucting system is shown

Sex differentiation
 Testosterone is required for Wolffian duct development in the female rabbit
 o Testosterone is produced by Leydig cells
o WD derivatives include epididymis, prostate, etc
 MIH: Mullerian inhibitory substance is required for the regression of the Mullerian duct; produced by Sertoli
cells. Wolffian duct is maintained in males.