Trichostatin A, an epigenetic modifier, mitigates radiation-induced androphysiological anomalies and metabolite changes in mice as evident from NMR-based metabolomics

Purpose: Ionizing radiation is known to damage male reproductive system. Current study aims to study the mitigative effects of trichostatin A on male reproductive system and accompanying metabolite changes in testicular tissue of mice. Materials and methods: Eight-week-old male C57 Bl/6J mice were exposed to 2 Gy γ-radiation with or without trichostatin A administration. The animals were sacrificed at various time intervals for organ body weight index, sperm head abnormality assay, sperm mobility assay, and study of various metabolites in testicular tissue using NMR spectroscopy. Results: Ionizing radiation induced no significant change in organ body weight index at any time points studied, however a significant increase in sperm head abnormality and significant decrease in sperm mobility was evident on fifth postirradiation week. trichostatin A administration, 1 and 24 h postirradiation, could efficiently mitigate radiation-induced changes studied. NMR metabolome profile also showed prominent changes associated with energy metabolism, osmolytes and membrane metabolism at 24 h postirradiation and some of these changes (choline, glycerolphosphoethanol amine, and glycine) were persistent till fifth postirradiation week. Trichostatin A administration resulted in reverting metabolic profile of the irradiated animals to normal level suggesting its mitigative role. Conclusion: Results obtained suggest that trichostatin A could restore normal metabolic profile of testicular tissue of irradiated male mice and also restored certain morphological and functional properties of sperms. Trichostatin A thus could further be exploited for its radio-mitigative properties.