Effects of psychosocial stress on the expression and cellular localization of TET2 methylcytosine dioxygenase in germ cells of male mice

Psychosocial stress is a major risk factor for various health issues, including male reproductive dysfunction. We previously reported that chronic social defeat stress (cSDS), a well-established animal model of psychosocial stress, alters DNA methylation profiles in male mouse germ cells; however, the upstream enzymatic dynamics remain poorly understood. In the present study, we evaluated the effects of cSDS on the expression of DNA methyltransferase (DNMT) and Ten-eleven-translocation (TET) methylcytosine dioxygenase family enzymes in male germ cells. Exposure to cSDS significantly and selectively upregulated Tet2 transcript and TET2 protein levels in isolated total germ cells, accompanied by elevated total TET enzymatic activity, whereas DNMT family expression remained unchanged. To further delineate this response, we performed quantitative immunofluorescence analysis using PNA-lectin and DAPI co-staining to characterize the spatial localization of TET2 during spermatogenesis. Nuclear TET2 signals were observed in spermatogonia, meiotic spermatocytes, and round and elongated spermatids, and cSDS exposure prominently enhanced TET2 intensity in round spermatids during seminiferous tubule stages VII and VIII. These findings demonstrate that psychosocial stress upregulates TET2 expression in a seminiferous tubule stage- and spermatogenic cell-type-specific manner, uncovering a key enzymatic component associated with stress-induced germline epigenetic remodeling.