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

Abstract

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.

Keywords:

• Ionizing radiation
• male reproductive system
• 1H NMR
• metabolome
• trichostatin A
• mitigation

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The work was supported by DRDO, Govt. of India. TH was supported by a Department of Science and Technology (DST, India) fellowship (DST Inspire) and KM was supported by University Grants Commission (UGC), India for carrying out research, [INM 313].

Notes on contributors

Teena Haritwal

Teena Haritwal is a DST sponsored researcher currently working on radiation effects on mice reproductive system.

Kiran Maan

Kiran Maan is a UGC sponsored researcher currently working on radiation induced metabolomic changes in mice.

Poonam Rana

Poonam Rana, PhD, is Scientist E in NMR Research Centre, INMAS and currently involved in identification of imaging and metabolic markers for radiation stress using advanced MR techniques. Her area of research interest include MR imaging, metabolomics and NMR spectroscopy.

Suhel Parvez

Suhel Parvez, Professor and Head of Toxicology Department of Jamia Hamdard University, is keenly interested in behavioral biology of mice and other model organisms.

Ajay K. Singh

Ajay K. Singh is Director of INMAS, Delhi and his main interest is in nuclear medicine.

Subash Khushu

Subash Khushu is head of NMR research centre, INMAS and is interested in medical imaging and identification of metabolomic markers of stress.

Paban K. Agrawala

Paban K. Agrawala is keenly interested in the epigenetic alterations induced due to stress and radiation countermeasure development.