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In silico prediction of microRNAs on fluoride induced sperm toxicity in mice
Azhwar Raghunath1, Dhivyalakshmi Jeyabaskar1, Kiruthika Sundarraj1
1Molecular Toxicology Laboratory, Department of Biotechnology, Bharathiar University, Coimbatore, 641 046, Tamilnadu, India.
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.
Insights
Fluoride exposure causes male infertility by down-regulating critical genes. Researchers identified specific microRNAs (miRNAs) that may mediate this damage, offering potential biomarkers for diagnosis and new therapeutic targets for fluoride-induced infertility.
Area of Science:
- Reproductive Biology
- Toxicology
- Molecular Biology
Background:
- Fluorosis is a global health issue linked to male reproductive impairment.
- Fluoride (F) toxicity affects male fertility by down-regulating genes involved in crucial biological processes.
Purpose of the Study:
- To identify microRNAs (miRNAs) responsible for down-regulating genes affected by fluoride exposure.
- To explore the potential of these miRNAs as non-invasive biomarkers for fluoride-induced male infertility.
Main Methods:
- Utilized TargetScan, DIANA, and MicroCosm prediction tools to identify miRNAs targeting 63 fluoride-affected genes.
- Analyzed miRNA-mRNA interactions to construct a network illustrating molecular pathways.
- Cross-referenced predicted interactions with experimentally validated miRNA-gene targets in mice.
Main Results:
- Identified 3059 potential miRNA targets among the 63 affected genes.
- Found 11 miRNAs commonly predicted by all three tools.
- Confirmed seven specific miRNAs and their targeted genes with existing experimental data in mice, highlighting complex interactions leading to sperm dysfunction.
Conclusions:
- The predicted miRNAs provide insights into the molecular mechanisms of fluoride-induced male infertility.
- These miRNAs show potential as non-invasive biomarkers for assessing fluoride toxicity.
- Understanding miRNA pathways in fluoride intoxication may lead to novel therapeutic strategies, such as antagomirs, for fertility recovery.
