- Exposure to high-levels of fluoride causes reproductive toxicity in humans.
- Increased testes toxicity and inflammation were seen in a mouse model of fluorosis.
- The NaF-mediated testes toxicity and inflammation were absent in IL-17A -/- mice.
- In Leydig cells IL-17A and/or NaF increased apoptosis and decreased testosterone.
- Il-17A appears to mediate the effect of NaF and Leydig cells may be the target.
The reproductive toxicity of fluoride (F) has been verified by various epidemiological and experimental studies. Our previous work suggested that the interleukin 17A (IL-17A) is involved in the testicular damage induced by excessive F exposure. In this study, we further investigated the role of IL-17A in F-induced testicular injury. Wild type (WT) and IL-17A knockout (IL-17A-/-) mice were exposed to 0, 25, 50, or 100 mg/L sodium fluoride (NaF) for 90 days. We found that exposure to excessive F levels caused testicular damage, decreased semen quality, negatively affected testicular morphology, and increased the inflammatory response. Specifically, excessive F intake increased the expression levels of IL-17A in the testis and increased the protein levels of Act1, NF-kB, IL-17R, C/EBP-a, and TRAF6 in the IL-17A signaling pathway. The increase in IL-17A expression corresponded to increases expression of IL-17R, IL-6, IL-23, IL-1B, TGF-B and TNF-a as assessed by RT-PCR and ELISA assays. Remarkably, IL-17A knockout in mice ameliorated the effects of F on testicular damage, semen quality, testicular morphology, and the immune response. Additionally, we found the in vitro exposure of Leydig cells to NaF and recombinant IL-17A led to abnormal apoptosis and a decrease in testosterone secretion. Our findings prove that IL-17A plays a key role in the exacerbation of testicular injuries in F-exposed mice, and that IL-17A deficiency can alleviate F-induced injury by inhibiting the immune response and apoptosis in the testis. These data suggest that targeting IL-17A may be a useful therapeutic strategy for treating F-mediated toxicity in the testis.
Model of influence of IL-17A for fluoride-induced testis injury by boosting immune response in testis and apoptosis of Leydig cells. IL-17A and its signaling pathway might be involved in the regulation of testicular damage in fluorosis animals and the deletion of IL-17A could abrogate the lesion of testicular fluorosis, including the testicular morphology, semen quality and the ability of testosterone secretion. Additionally, excessive F intake may evoke immune response in testis and apoptosis of Leydig cells. Therefore, we concluded that Therefore, we concluded that IL-17A deficiency alleviate fluoride-induced injury by inhibiting immune response and apoptosis in testis.
*Original article online at https://www.sciencedirect.com/science/article/abs/pii/S0045653520323730?via%3Dihub
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