T-2 Toxin Caused Mice Testicular Inflammation Injury via ROS-Mediated NLRP3 Inflammasome Activation.

Abstract

T-2 toxin treatment causes male reproduction system dysfunction, although the exact mechanism remains unclear. In this research, male Kunming mice and TM4 cells were treated with varying concentrations of the T-2 toxin for evaluating the adverse effect of T-2 toxin on male reproductive function. MCC950 or NAC was used to block NLRP3 inflammasome activation and eliminate reactive oxygen species (ROS) accumulation in the TM4 cell, respectively. The results showed that: (1) T-2 toxin caused testicular atrophy, destroyed the microstructure and ultrastructure of the testis, and caused sperm deformities; (2) T-2 toxin increased the content and gene expressions of TNF-α and IL-6 and decreased the IL-10 content and gene expression, causing testis and TM4 cell inflammatory injury; (3) T-2 toxin activated NLRP3 inflammasome in the testis and TM4 cells and caused ROS accumulation in the testis; (4) suppressing NLRP3 inflammasome activation using 20 nM MCC950 alleviated the TM4 cell inflammatory damage caused via the T-2 toxin; nevertheless, 20 nM MCC950 did not reduce ROS accumulation in TM4 cells; and (5) NAC relieved the inflammatory damage in TM4 cells by inhibiting NLRP3 inflammasome activation. Taken together, T-2 toxin caused testicular inflammation injury through ROS-mediated NLRP3 inflammasome activation, resulting in male reproductive dysfunction.