Tetrabromobisphenol S (TBBPS) exposure induced the testicular aging through NLRP3-mediated inflammatory signaling pathway in vitro and in vivo

Abstract

Tetrabromobisphenol A (TBBPA) is an extensively employed Brominated flame retardant (BFR), but studies have shown that it has a range of toxicities, and it has been banned from use at present. Tetrabromobisphenol S (TBBPS) is increasingly used in industrial production as a substitute for TBBPA. However, up to now, the toxicity and molecular mechanism of TBBPS in the reproductive system have not been fully revealed. Therefore, we investigated the effects of TBBPS on testicular. In vitro, GC-1 cells and TM4 cells were used as models to perform an array of biochemical tests, and the toxicological impacts of TBBPS on testicular cells were evaluated. It was found that TBBPS could induce testicular cells senescence. Additionally, p16, p21, and p53 expression were also increased after TBBPS treatment. TBBPS also induced oxidative stress and inflammation response. Mechanistic studies have revealed that TBBPS causes mitochondrial damage, which leads to mitochondrial ds-DNA leakage into the cytoplasm, the NLRP3 inflammasome was then activated, in turn leading to inflammatory and senescence responses in testicular cells. In vivo, we found that TBBPS caused testicular tissue aging and inflammatory responses by detecting a series of molecular markers. In summary, the current study demonstrates that TBBPS can induce aging damage and inflammatory responses in testis, and this study lays a foundation for further exploring the reproductive toxicity of TBBPS.