title: In silico prediction of microRNAs on fluoride induced sperm toxicity in mice.
abstract: 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.
authors.affiliation: Molecular Toxicology Laboratory, Department of Biotechnology, Bharathiar University, Coimbatore, 641 046, Tamilnadu, India.
authors.forename: Azhwar
authors.initials: A
authors.lastname: Raghunath
authors.affiliation: Molecular Toxicology Laboratory, Department of Biotechnology, Bharathiar University, Coimbatore, 641 046, Tamilnadu, India.
authors.forename: Dhivyalakshmi
authors.initials: D
authors.lastname: Jeyabaskar
authors.affiliation: Molecular Toxicology Laboratory, Department of Biotechnology, Bharathiar University, Coimbatore, 641 046, Tamilnadu, India.
authors.forename: Kiruthika
authors.initials: K
authors.lastname: Sundarraj
authors.affiliation: Molecular Toxicology Laboratory, Department of Biotechnology, Bharathiar University, Coimbatore, 641 046, Tamilnadu, India.
authors.forename: Lakshmikanthan
authors.initials: L
authors.lastname: Panneerselvam
authors.affiliation: Molecular Toxicology Laboratory, Department of Biotechnology, Bharathiar University, Coimbatore, 641 046, Tamilnadu, India. Electronic address: ekas2009@buc.edu.in.
authors.forename: Ekambaram
authors.initials: E
authors.lastname: Perumal
mesh_terms: D000818:Animals; D003198:Computer Simulation; D005459:Fluorides / Q000633:toxicity*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects*; D013094:Spermatozoa / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger; D005459:Fluorides
keywords: Biomarker; Fluoride toxicity; Gene regulatory network; Male infertility; Sperm; miRNA-mRNA interaction; microRNA