Cadmium exposure induces pyroptosis in testicular tissue by increasing oxidative stress and activating the AIM2 inflammasome pathway

High doses of cadmium (Cd) cause irreversible injury to the reproductive system, especially testicular tissue. Studies have shown that pyroptosis is involved in Cd-induced tissue damage, but whether pyroptosis is involved in damage to testicular tissue following Cd exposure remains unclear. To investigate the mechanism of pyroptosis in testicular injury induced by Cd exposure, we used 8-week-old male C57BL/6J mice subjected to consecutive 7 days of intraper-itoneal injection of cadmium chloride (CdCl2) at concentrations of 0, 1.0 and 3.0 mg/kg. The results indicated that 3.0 mg/kg CdCl2 significantly decreased serum testosterone levels, sperm concentration and sperm motility, while in-creased LDH and IL-1 beta levels. Testicular HE staining indicated that Cd exposure damaged the interstitial cells and in-creased the atypical residual bodies. Fluorescence results indicated that 3.0 mg/kg CdCl2 increased ROS levels, DNA damage, and the number of TUNEL-positive seminiferous tubule cells in testicular tissue. Transcriptome analysis showed that Cd exposure mainly induced inflammatory and chemokine signaling pathways in testicular tissue, with upregulated mRNA levels of Aim2, and reduced mRNA levels of Nlrp3. Further analysis showed that 3.0 mg/kg CdCl2 increased the expression of testicular HO-1, SOD2, gamma H2AX and PARP-1, as well as the pyroptosis-related factors GSDMD, GSDME, Caspase-1, ASC and IL-1 beta. In conclusion, our results provide a possible mechanism by which Cd exposure activates the AIM2 pathway by increasing oxidative stress injury to induce pyroptosis in testicular tissue. This provides a new perspective on testicular damage caused by Cd exposure.

Automated summary

High doses of cadmium exposure lead to irreversible damage to the testicular tissue, mainly through the activation of pyroptosis pathway. The exposure of Cd significantly decreases testosterone levels, sperm concentration and sperm motility, while increasing LDH and IL-1 beta levels. The transcriptome analysis shows that Cd exposure induces inflammatory and chemokine signaling pathways in the testicular tissue.