Multivitamin supplementation mitigates chronic stress induced testicular dysfunction by restoring one-carbon metabolism, redox balance, and spermatogenesis in rats.

Male reproductive capability suffers from prolonged psychological stress, which also proves to be a potential factor behind infertility problems. The common use of selective serotonin reuptake inhibitors SSRIs needs to be replaced with safer antidepressant options because their reproductive side effects create a requirement for such alternatives. Current study examined how multivitamin supplements protect against testicular dysfunction that occurs due to stress in a study using a rat model of chronic unpredictable mild stress (CUMS). For 21 days, researchers assigned male Sprague Dawley rats to three groups: a control group, a stressed group, and a stressed group that received multivitamin treatment with L-methyl folate, vitamin D3, and vitamin B2. CUMS caused a significant increase in anhedonic behavious, serum cortisol and testosterone levels, which resulted in damaged seminiferous tubule structure and decreased spermatogenic cell counts, together with Johnsen's score and alterations in testicular structure. In stressed untreated group, testicular levels of folate and global DNA methylation declined, together with increased oxidative stress and inflammatory marker expression changes and decreased expression of genes that control cell proliferation, meiosis, and sperm motility. The biochemical, histological, epigenetic and molecular changes that occurred during the study were all reversed by multivitamin supplementation. These data show that multivitamin supplementation helps prevent testicular damage caused by stress because it restores hormonal balance, together with redox status and one-carbon metabolism and spermatogenesis, while supporting the use of multivitamin-based treatments as a potential additional method to maintain male reproductive health during chronic stress periods.