From animal to cell model: Pyroptosis targeted-fibrosis is a novel mechanism of lead-induced testicular toxicity

Lead (Pb) exists widely in soil and seriously threatens agricultural soil and food crops. Pb can cause serious damage to organs. In this study, the animal model of Pb-induced rat testicular injury and the cell model of Pb-induced TM4 Sertoli cell injury were established to verify whether the testicular toxicity of Pb was related to pyroptosis-mediated fibrosis. The results of experiment in vivo showed that Pb could cause oxidative stress and up-regulated the expression levels of inflammation, pyroptosis, and fibrosis-related proteins in the testis of rats. The results of experiments in vitro showed that Pb induced the cell damage, enhanced the reactive oxygen species level in the TM4 Sertoli cells. After using nuclear factor-kappa B inhibitor and Caspase-1 inhibitor, the elevation of TM4 Sertoli cell inflammation, pyroptosis, and fibrosis-related proteins induced by Pb exposure was significantly decreased. Taken together, Pb can cause pyroptosis-targeted fibrosis and ultimately issues in testicular damage. [Display omitted] •Pb exposure causes testicular injury in rats.•Pb exposure induces damage to TM4 sertoli cells.•Pb leads to testicular pyroptosis through activation of the NF-κB signaling pathway.•Pb leads to testicular fibrosis by inducing Caspase-1-dependent pyroptosis.