Sry-Independent Overexpression of Sox9 Supports Spermatogenesis and Fertility in the Mouse.

Biology of reproduction

PubMedID: 26536904

Ortega EA, Ruthig VA, Ward MA. Sry-Independent Overexpression of Sox9 Supports Spermatogenesis and Fertility in the Mouse. Biol Reprod. 2015;.
The Y chromosome gene Sry is responsible for sex determination in mammals and initiates a cascade of events that direct differentiation of bipotential genital ridges toward male-specific fate. Sox9 is an autosomal gene and a primary downstream target of SRY. The activation of Sox9 in the absence of Sry is sufficient for initiation of male-specific sex determination. Sry- to -Sox9 replacement has mostly been studied in the context of sex determination during early embryogenesis. Here, we tested whether Sry- to -Sox9 replacement affects male fertility in adulthood. We examined males with the Y chromosome carrying a deletion removing the endogenous Sry, with testes determination driven either by the Sox9 (XY (Tdym1)Sox9 ) or the Sry (XY (Tdym1)Sry ) transgenes as well as wild-type males (XY). XY (Tdym1)Sox9 males had reduced testes size, altered testes shape and vasculature, and increased incidence of defects in seminiferous epithelium underlying the coelomic blood vessel region when compared to XY (Tdym1)Sry and XY. There were no differences between XY (Tdym1)Sry and XY (Tdym1)Sox9 males in respect to sperm number, motility, morphology, and ability to fertilize oocytes in vitro, but for some parameters, transgenic males were impaired when compared to XY. In fecundity trials, XY (Tdym1)Sry, XY (Tdym1)Sox9, and XY males yielded similar average numbers of pups and litters. Overall, our findings support that males lacking the testis determinant Sry can be fertile and reinforce the notion that Sry does not play a role in mature gonads. Although transgenic Sox9 overexpression in the absence of Sry results in certain testicular abnormalities, it does not translate into fertility impairment.