Effects of fluoride on PIWI-interacting RNA expression profiling in testis of mice

Excessive fluoride intake can damage testis by breaking the integrity of sperm DNA and changing the expression profiles of testicular mRNAs and microRNAs. However, the effects of fluoride on the expression of PIWI-interacting RNAs (piRNAs) in mouse testes have not been reported. In this study, we determined the effect of fluoride on PIWI-interacting RNA expression profiling in testis of mice, using deep-sequencing technology. Compared to the control, 50 mg/L sodium fluoride (NaF) exposure led to a reduced testicular organ coefficient, semen quality, and testosterone level, and altered the testicular microstructure. Furthermore, NaF exposure also changed the expression of 28 piRNAs that regulate 182 target genes in mouse testes. In mice given water containing 50 mg/L NaF, the following four pathways were enriched and overexpressed: lysosomal, Jak-STAT, chemokine, and ubiquitin-mediated proteolysis. Among the piRNAs affecting the lysosomal pathway, piR-mmu-1277316, piR-mmu-8060747, and piR-mmu-1566415 levels were increased. We also observed increased levels of the following target gene mRNAs in lysosomal pathwa in the 50 mg/L NaF-treated group: Gga2, Ap4e1, Gla, and Ap1s3. These findings are in line with the results of piRNA-sequencing and suggest that piRNAs in the testis could be potential biomarkers for fluoride reproductive toxicity. Putative piRNA mediated mechanisms underlying fluoride-induced testis toxicity. Fluoride can induce testicular damage through altered piRNA expression in the testes and by mediating lysosomal, Jak-STAT, chemokin, and ubiquitin-mediated proteolysis pathways that affect post-transcriptional regulation. [Display omitted] •Excessive fluoride intake damaged the testis and altered the expression of piRNA.•Altered piRNA expression profile is involved in 28 piRNAs and 182 target genes.•The lysosomal signaling pathway were verified the biomarkers for fluorosis.