Fluorosis is an endemic global problem causing male reproductive impairment. F mediates male reproductive toxicity in mice down-regulating 63 genes involved in diverse biological processes - apoptosis, cell cycle, cell signaling, chemotaxis, electron transport, glycolysis, oxidative stress, sperm capacitation and spermatogenesis.
We predicted the miRNAs down-regulating these 63 genes using TargetScan, DIANA and MicroCosm. The prediction tools identified 3059 miRNAs targeting 63 genes. Of the predicted interactions, 11 miRNAs (mmu-miR-103, -107, -122, -188a, -199a-5p, -205, -340-5p, -345-3p, -452-5p, -499, -878-3p) were commonly found in the three tools utilized and seven miRNAs (miR-9-5p, miR-511-3p, miR-7b-5p, miR-30e-5p, miR-17-5p, miR-122-5p and miR-541-5p) targeting six genes (Traf3, Rock2, Rgs8, Atp1b2, Cacna2d1 and Aldoa) were already validated experimentally in mice. The miRNA-mRNA network of the predicted miRNAs with its respective targets revealed the complex interaction within a biological process leading to sperm dysfunction on exposure to F. Our findings not only suggest that the predicted miRs furnish evidence, but also have the potential to serve as non-invasive biomarkers on F-induced sperm dysfunction. Our data contribute towards elucidating the function of miRNAs in the fluoride induced infertility. miRNA molecular pathways in F intoxication will open new avenues on the use of antagomirs in recovering fertility.
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 2016 Mar 21 [Epub ahead of print]
Azhwar Raghunath, Dhivyalakshmi Jeyabaskar, Kiruthika Sundarraj, Lakshmikanthan Panneerselvam, Ekambaram Perumal
Molecular Toxicology Laboratory, Department of Biotechnology, Bharathiar University, Coimbatore, 641 046, Tamilnadu, India., Molecular Toxicology Laboratory, Department of Biotechnology, Bharathiar University, Coimbatore, 641 046, Tamilnadu, India., Molecular Toxicology Laboratory, Department of Biotechnology, Bharathiar University, Coimbatore, 641 046, Tamilnadu, India., Molecular Toxicology Laboratory, Department of Biotechnology, Bharathiar University, Coimbatore, 641 046, Tamilnadu, India., Molecular Toxicology Laboratory, Department of Biotechnology, Bharathiar University, Coimbatore, 641 046, Tamilnadu, India.