Aflatoxin B1-Induced Testosterone Biosynthesis Disorder via the ROS/AMPK Signaling Pathway in Male Mice

The worldwide prevalence of Aflatoxin B1 (AFB₁), which contaminates feedstock and food, is on the rise. AFB₁ inhibits testosterone (T) biosynthesis, but the mechanism is not yet clear. By establishing in vivo and in vitro models, this study found the number of Leydig cells (LCs), T content, and the expression of T biosynthesis key enzymes were suppressed after AFB₁ treatment. AFB₁ exposure also increased reactive oxygen species (ROS) and promoted mitochondrial injury and mitochondrial pathway apoptosis. Moreover, the AMPK signaling pathway was activated, and using an AMPK inhibitor relieved apoptosis and the suppressed T biosynthesis key enzymes of LCs caused by AFB₁ through regulating downstream p53 and Nur77. Additionally, adding ROS intervention could inhibit AMPK activation and alleviate the decreased T content caused by AFB₁. In summary, AFB₁ promotes the apoptosis of LCs and inhibits T biosynthesis key enzyme expression via activating the ROS/AMPK signaling pathway, which eventually leads to T synthesis disorder.