The excess fluoride intake has been shown to adversely affect male reproductive health. The aim of the present study was to investigate the key mechanism underlying fluoride-induced testicular dysfunction and the role of melatonin as a modulator of testicular metabolic, oxidative, and inflammatory load. The present results indicated that sodium fluoride (NaF) exposure to adult male golden hamsters severely impairs reproductive physiology as evident from markedly reduced sperm count/viability, testosterone level, androgen receptor (AR), testicular glucose transporter (GLUT-1), gap junction (connexin-43), and survival (Bcl-2) protein expression. NaF exposure markedly increased testicular oxidative load, inflammatory (NF-kB/COX-2), and apoptotic (caspase-3) protein expression. However, melatonin treatment remarkably restored testicular function as evident by normal histoarchitecture, increased sperm count/viability, enhanced antioxidant enzyme activities (SOD and Catalase), and decreased lipid peroxidation (LPO) level. In addition, melatonin treatment upregulated testicular Nrf-2/HO-I, SIRT-1/ FOXO-1, and downregulated NF-kB/COX-2 expression. Further, melatonin ameliorated NaF-induced testicular metabolic stress by modulating testicular GLUT-1expression, glucose level, and LDH activity. Furthermore, melatonin treatment enhanced testicular PCNA, Bcl-2, connexin-43, and reduced caspase-3 expression. In conclusion, we propose the molecular mechanism of fluoride-induced testicular damages and ameliorative action(s) of melatonin.
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Authors are thankful to the Council of Scientific and Industrial Research (CSIR), New Delhi, Government of India for providing financial support as Junior Research Fellowship (JRF) to Mr. Jitendra Kumar (grant scheme number: 09/013/(0709)/2017-EMR-I) and the University Grants Commission, New Delhi, India through CAS in Department of Zoology, Banaras Hindu University. The instrument subsidiary award from the Alexander von Humboldt Foundation, Bonn, Germany to Prof. Chandana Haldar is gratefully acknowledged.
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Kumar, J., Haldar, C. & Verma, R. Fluoride Compromises Testicular Redox Sensor, Gap Junction Protein, and Metabolic Status: Amelioration by Melatonin. Biol Trace Elem Res 196, 552–564 (2020). https://doi.org/10.1007/s12011-019-01946-6
- Nrf-2/HO-1/SIRT-1/ FOXO-1/NF-kB/COX-2