Sox9-dependent expression of Gstm6 in Sertoli cells during testis development in mice

Abstract

Glutathione S-transferases (GSTs) are an important family of multifunctional enzymes that play a role in the protection of tissues by the detoxification of hazardous and carcinogenic compounds. We found previously that Gstm6 is upregulated in the somatic cells of male mouse fetal gonads relative to female gonads. In this study, we describe the spatial and temporal expression pattern of Gstm6 during mouse development. We show that Gstm6 is predominantly expressed in the reproductive system, at significantly higher levels in XY gonads compared with XX gonads from 11.5 dpc onwards, and remains expressed in the testes in adult mice. Its expression is associated with the Sertoli cell lineage, and is dependent on the expression of the male sex-determining gene Sox9. Our data suggest that Gstm6 plays a male-specific role in gonad development or function, possibly by modulating the exposure of somatic tissue and/or germ cells to endogenous or exogenous toxicants.

Differential Regulation of TLE3 in Sertoli Cells of the Testes during Postnatal Development

“…One of the main functions of Sertoli cells is self-renewal of spermatogonial stem cells and regulation of spermatocyte differentiation [41]. On PD10, the spermatogonial stem cells and Sertoli cells are seen in the seminiferous tubules of mouse testes [13,49]. Interestingly, our results also showed that the expression of TLE3 begins to appear in Sertoli cells of PD10 mice (Figure 2c) and remained high post–testicular development.…”

“…Additionally, Sertoli cells are in contact with germ cells for communication and to increase their surface area in seminiferous tubules [9]. Although recent studies have identified genes regulating the functions of Sertoli cells in spermatogenesis [3,6,9,10,11,12,13,14,15], additional studies are required to understand the role of Sertoli cells in male reproduction and fertility.…”

Claudin 11 Deficiency in Mice Results in Loss of the Sertoli Cell Epithelial Phenotype in the Testis1

“…Microarray data from these animals reveal an induction of detoxification machinery in Sertoli cells (upregulation of Gstm1 and Gstm6 [48,49]) and a suppression of detoxification machinery in germ cells (downregulation of Gstm3 [50]). It is tempting to speculate that these changes may constitute an initial trigger for germ cell apoptosis.…”

Uncovering Gene Regulatory Networks During Mouse Fetal Germ Cell Development

“…In the complete absence of germ cells, as in the case of W v /W v gonads, supporting cells in the ovary develop into pre-follicles but subsequently degenerate [61,62]. One might expect that in the absence of germ cells, relative expression of somatic genes would be increased due to a loss of dilution effect, but in practice, this phenomenon is observed only marginally [33,34]. From the present screen, however, expression of some genes was clearly detected at higher levels in mutant ovaries than in wild-type ovaries and may be genuinely up-regulated in somatic cells in the absence of germ cells.…”

“…This genetic model is commonly used to show that a gene is expressed either in somatic cells (i.e., detected in both wild-type and mutant gonads) or in germ cells (i.e., detected in wild-type gonads only) [33,34]. In this study, we compared the transcriptomes of W v /W v with wild-type gonads at several stages in order to highlight genes specifically or preferentially expressed in somatic versus germ cells.…”