Background: The SRY/Sry gene is expressed in pre-Sertoli cells of the male genital ridge and functions as the mammalian testis determining factor (TDF). In addition, expression of SRY/Sry outside the genital ridge has been reported, including preimplantation embryos, although the functional significance of this is not well understood. Results: Using Cre-mediated lineage studies and transgenic reporter mouse models, we now show that promoter sequences of human, pig and mouse SRY drive robust reporter gene expression in epiblast cells of peri-implantation embryos between embryonic day (E) 4.5 and E6.5. Analysis of endogenous Sry expression revealed that linear transcripts are produced by means of multiple polyadenylation sites in E4.5 embryos. Within the epiblast, SRY reporter expression mimics the expression seen using a Gata4 reporter model, but is dissimilar to that seen using an Oct4 reporter model. In addition, we report that overexpression of mouse Sry in embryonic stem cells leads to down-regulation of the core pluripotency markers Sox2 and Nanog. Conclusion: We propose that SRY/Sry may function as a male-specific maturation factor in the peri-implantation mammalian embryo, providing a genetic mechanism to help explain the observation that male embryos are developmentally more advanced compared with female embryos, and suggesting a role for SRY beyond that of TDF. Developmental Dynamics 241:1192-1204, 2012. V C 2012 Wiley Periodicals, Inc.Key words: SRY; promoter; blastocyst; epiblast; male-specific maturation factor; pluripotency; Sox2; Oct4; Nanog
Key findings:The proximal promoter of SRY/Sry from several mammalian species (pig, human and mouse) directs reporter gene expression in the epiblast of pre-and peri-implantation mouse embryos. Expression levels of SRY/Sry reporters coincide with the maturation stage of pre-and peri-implantation embryos, being positively correlated with a Gata4 reporter and negatively correlated with an Oct4 reporter. Overexpression of Sry in murine embryonic stem cells results in reduced expression of the pluripotency markers Sox2 and Nanog.