Lycopene Alleviates T-2 Toxin-Induced Testosterone Synthesis Disorder by Inhibiting ROS/p38/TORC2/CREB Axis.

T-2 toxin is a typical fusarium mycotoxin that induces reproductive injury. As a male reproductive toxicant, impaired testosterone biosynthesis is the primary reproductive toxic effect induced by T-2 toxin. Therefore, clarifying how T-2 toxin disrupts testosterone synthesis at the molecular level and screening natural plant extracts that can alleviate this reproductive toxicity are of great importance. Lycopene (LYC) is a natural carotenoid known for its reproductive protective properties. Hence, this work assessed the protective efficacy and molecular mechanisms of LYC against T-2 toxin-caused testosterone synthesis disruption. Our results showed that LYC supplementation significantly alleviated testicular structural injury, restored testicular organ coefficients, and rescued serum and intracellular testosterone levels via transcriptional and translational upregulation of key steroidogenic proteins. Mechanistically, LYC suppressed T-2 toxin-triggered reactive oxygen species (ROS) accumulation, inhibited MAPK pathway activation, and prevented ROS/p38/TORC2/CREB axis activation, thereby restoring TORC2/CREB transcriptional activity and steroidogenesis. Pharmacological validation using SB203580 and NAC confirmed the central role of the ROS/p38/TORC2/CREB axis. Taken together, LYC alleviates T-2 toxin-triggered disruption of testosterone synthesis by inhibiting the ROS/p38/TORC2/CREB axis, and we identify LYC as a promising nutritional strategy against mycotoxin-caused reproductive toxicity.