IL-17A deficiency alleviate fluoride-induced injury by inhibiting immune response and apoptosis in testis

Backgroud Reproductive toxicity of fluoride (F) has been verified by epidemiological and experimental investigations. Based on the literature and our recent studies, as well as the reports inferred by sequencing analysis of mice with normal and fluorosis testes, it is suggested that the interleukin 17A (IL-17A) signaling pathway may be the key link of the damage in testes of the fluorosis animals. To investigate the role of IL-17A in the process of F-induced testicular injury, we exposed wild type (WT) genotype mice and IL-17A knockout (IL-17A-/-) genotype mice to 50mg/L Sodium fluoride (NaF) at 90 days, respectively.Results From the results, we verified IL-17A played a key role in the exacerbation of testicular injuries in fluoride-exposed animals, and found IL-17A knockdown could evidently ameliorate the lesion of testicular damage, including the improves in semen quality,maintain testicular morphology and reducing the immune response in testis. In addition, our results showed that Leydig cells exposed to NaF and recombinant IL-17A in vitro displayed both abnormal apoptoses and decreased secretions of testosterone.Conclusions Altogether, our findings proved that IL-17A deficiency alleviate fluoride-induced injury by inhibiting immune response and apoptosis in testis. This study also provides the mechanism of reproductive toxicity of F, the basis for scientific diagnosis, and possible target drug design.