Mus musculus musculus Transcriptome or Gene expression

Male fertility relies on spermatogenesis, a complex process of germ cell differentiation that is regulated by genetic and environmental factors. Environmental hypoxia adversely affects reproductive health in humans and impairs spermatogenesis in mice. However, a detail analysis of hypoxia induced changes in gene expression is still lacking and a complete fertility evaluation of hypoxia exposed animals and their offspring awaits investigation. In this study, a hypobaric hypoxic chamber was used to simulate hypoxic conditions in mice and effects of hypoxia on spermatogenesis, fertility and testicular gene expression were evaluated. The results showed that hypoxia exposure reduced the number of undifferentiated spermatogonia but did not changed the regenerative capacity of spermatogonial stem cells after transplantation. Sperm morphological analysis showed that hypoxia exposure significantly increased the percent of abnormal sperm and these defects were recovered 2 months after hypoxia treated animals were raised in control conditions. Transcriptome analysis of testicular tissues from control and hypoxia treated animals revealed that 766 genes were up-regulated and 965 genes were down-regulated by hypoxia exposure. Surprisingly, we observed that the expression of genes regulating epigenetic modifications were altered, indicating hypoxia-induced damage to spermatogenesis may be intergenerational. Interestingly, we examined testis of animals sired by hypoxia exposed male mice and detected impaired spermatogenesis in the offspring. Together, these findings suggest that hypoxia exposure changes testicular gene expression and causes long-lasting damage to spermatogenesis.