Chronic social defeat stress alters DNA methylation profiles of male germ cells in mice

Abstract

Chronic exposure to stress disrupts various structural and functional features in living organisms. In addition to the adverse effects of chronic stress on the central nervous system, evidence suggests that chronic stress leads to dysfunction of the male reproductive system. In particular, previous reports have shown that exposure to chronic social defeat stress (cSDS), an animal model of psychosocial stress and depression, induces a reduction in sperm concentration and motility. However, the mechanism by which exposure to cSDS contributes to male reproductive abnormalities remains poorly understood. In the present study, we investigated the effects of cSDS on DNA methylation profiles in germ cells isolated from the testes of C57BL/6J mice. We found that exposing mice to cSDS significantly decreased the 5-methylcytosine levels but not 5-hydroxymethylcytosine levels in germ cells. Furthermore, reduced representation of bisulfite sequencing revealed that cSDS exposure specifically alters the DNA methylation status at gene regulatory regions of transcriptional regulation-related genes. These findings suggest that chronic exposure to psychosocial stress disrupts the male reproductive system through abnormal epigenetic modifications in male germ cell, providing novel insight into the detrimental effects of chronic stress on male germ cell development in the testis.