T-2 toxin-induced testicular impairment by triggering oxidative stress and ferroptosis.

T-2 toxin is a trichothecene mycotoxin of significant danger to humans and animals. Its impact on reproductive toxicity is attributed to oxidative stress, which ultimately leads to cell death. Ferroptosis is a programmed cell death that characterized by lipid peroxidation. This study aimed to investigate the toxic effects of T-2 toxin on mouse testis and the potential mechanism of T-2 toxin-induced ferroptosis. T-2 toxin significantly altered the morphology of the testis and decreased testosterone level, sperm concentration, and increased sperm malformation rate, as well as induced oxidative damage with reactive oxygen species and malondialdehyde accumulated, and activity of superoxide dismutase, glutathione peroxidase decreased. Additionally, T-2 toxin induced ferroptosis by accumulating iron ions, increasing prostaglandin endoperoxide synthase 2, downregulating glutathione peroxidase 4 and ferritin heavy chain 1, as well as manifesting ferroptotic morphological alterations, ultimately leading to testicular impairment. Administration of ferroptosis inhibitor liproxstatin-1 or antioxidant resveratrol effectively mitigated the T-2 toxin-induced ferroptosis and testicular injury. These findings provided novel insights into the fundamental mechanism of T-2 toxin-induced cell death and furnished further proof of the potential therapeutic effect in addressing T-2 toxin-induced testicular impairment.