Vitamin D alleviates chronic stress-induced testicular steroidogenesis disruption in Wistar rats.

Stress is associated with various health issues. Research has highlighted the relationship between chronic stress and male reproductive health. One of the primary mechanisms underlying stress-induced male reproductive dysfunction is impaired steroidogenesis. In the present study, we validated a chronic unpredictable stress (CUS) model and investigated testicular dysfunction in CUS rats. The CUS paradigm involved exposing rats to a variety of stressors daily for 8 weeks. Vitamin D (10 µg/kg/twice a week, p.o) was administered to CUS rats starting 2 weeks after the onset of stress exposure and continued until the end of study. The stress in rats was confirmed by the occurrence of anxiety and depressive-like behaviours through elevated plus-maze test & novelty-suppressed feeding test and rise in serum corticosterone levels. Testicular dysfunction in CUS rats was assessed via serum gonadotropins, testosterone, cytokines, oxidative stress, and testis-epididymis-sperm morphology. The reduction in steroidogenesis was confirmed via immunohistochemical analysis of 17β-hydroxysteroid dehydrogenase-3 (17β-HSD3), steroidogenic acute regulatory gene (StAR) and vitamin D receptor (VDR) expression. Further, we studied the role of vitamin D in alleviating stress-induced testicular damage and the potential mechanisms underlying steroidogenic alterations in CUS rats. Notably, vitamin D treatment prevented CUS-induced decline in testicular 17β-HSD3, StAR and VDR expression. Moreover, vitamin D ameliorated the CUS-induced reduction in serum testosterone levels. Histological assessment revealed that vitamin D prevented CUS-induced damage in sperm, testis and epididymis morphology. In conclusion, our findings suggest that CUS exposure induces testicular dysfunction, which can be prevented by vitamin D, potentially through the regulation of steroidogenic pathways.