Hypobaric hypoxia exposure alters transcriptome in mouse testis and impairs spermatogenesis in offspring

Male fertility relies on continual and robust spermatogenesis. Environmental hypoxia adversely affects reproductive health in humans and animal studies provide compelling evidences that hypoxia impairs spermatogenesis in directly exposed individuals. However, a detail examination of hypoxia induced changes in testicular gene expression is still lacking and spermatogenesis in offspring of hypoxia exposed animals of 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 change the regenerative capacity of spermatogonial stem cells (SSCs) after transplantation. Hypoxia significantly increased the percent of abnormal sperm and these defects were recovered 2 months after returning to the normoxia. Transcriptome analysis of testicular tissues from control and hypoxia treated animals revealed that 766 genes were up-regulated and 965 genes were down-regulated. Surprisingly, expressions of genes that regulate epigenetic modifications were altered, indicating hypoxia-induced damage to spermatogenesis may be intergenerational. Indeed, animals that were sired by hypoxia exposed males exhibited impaired spermatogenesis. Together, these findings suggest that hypoxia exposure alters testicular gene expression and causes long-lasting damage to spermatogenesis.