Sox8 is a critical regulator of adult Sertoli cell function and male fertility

Abstract

Sox8 encodes a high-mobility group transcription factor that is widely expressed during development. Sox8, -9 and -10 form group E of the Sox gene family which has been implicated in several human developmental disorders. In contrast to other SoxE genes, the role of Sox8 is unclear and Sox8 mouse mutants reportedly showed only idiopathic weight loss and reduced bone density. The careful analysis of our Sox8 null mice, however, revealed a progressive male infertility phenotype. Sox8 null males only sporadically produced litters of reduced size at young ages. We have shown that SOX8 protein is a product of adult Sertoli cells and its elimination results in an age-dependent deregulation of spermatogenesis, characterized by sloughing of spermatocytes and round spermatids, spermiation failure and a progressive disorganization of the spermatogenic cycle, which resulted in the inappropriate placement and juxtaposition of germ cell types within the epithelium. Those sperm that did enter the epididymides displayed abnormal motility. These data show that SOX8 is a critical regulator of adult Sertoli cell function and is required for both its cytoarchitectural and paracrine interactions with germ cells.

Adult-onset degeneration of adipose tissue in mice deficient for the Sox8 transcription factor

“…Food intake and body weight over the five-day period are shown as percent of the respective values at the onset of the experiment. reduction in adipose tissues is a consequence of the progressive infertility observed in Sox8-deficient males at older ages (23), because alterations in the adipose tissue precede those in the testis and are also observed in females which do not exhibit any fertility problems. We thus have to conclude that the reduction of adipose tissues represents an independent phenotype in Sox8-deficient mice.…”

“…1A). On a C57Bl/6J background, the osteopenic phenotype of Sox8-deficient mice is much more pronounced (25) and Sox8-deficient males have been reported to develop progressive infertility with increasing age (23). To avoid confounding effects from the osteopenic phenotype and potential breeding problems, we performed our study with mice on a mixed background.…”

“…Sox8-deficient mice were viable and able to produce offspring (22), although males developed sterility at older ages (23). Dramatic phenotypic manifestations are also not apparent in humans with SOX8 deletions.…”

Mrhl Long Noncoding RNA Mediates Meiotic Commitment of Mouse Spermatogonial Cells by Regulating Sox8 Expression

“…Sox8 is an important transcription factor during spermatogenesis due to its crucial function in Sertoli cells (30,31). However, there are no reports of Sox8 expression in testicular germ cells.…”

Transcription and post-transcriptional regulation of spermatogenesis

“…SOX9 and another group-E family member, SOX8, are both expressed in adult Sertoli cells, leading to the possibility that, like WT1 and RHOX5, these SOX transcription factors function in Sertoli cells to drive spermatogenesis. While this has not been addressed in the case of SOX9, recently O'Bryan et al (2008) examined this issue for SOX8. They found that disruption of the Sox8 gene elicits an age-dependent perturbation of spermatogenesis, characterized by sloughing of spermatocytes and round spermatids, failure in spermiation, disorganization of the spermatogenic cycle and disorientation and inappropriate placement of germ-cell types within the epithelium.…”