Tryptophan Metabolism as a Key Target in PFOS-Mediated Decline of Porcine Oocyte Quality

Perfluorooctanesulfonate (PFOS) is a persistent environmental endocrine disruptor that poses severe threats to mammalian reproductive health upon accumulation in organisms. Therefore, elucidating the mechanisms of PFOS-induced damage and identifying effective protective strategies are of critical importance. In this study, an untargeted metabolomic analysis revealed that PFOS exposure significantly disrupted metabolic homeostasis in oocytes. Using public databases to predict potential target proteins of PFOS and performing KEGG pathway enrichment analysis, we identified the tryptophan metabolism pathway as a key target of PFOS. Molecular docking and molecular dynamics simulations demonstrated specific binding between PFOS and proteins involved in the tryptophan metabolism pathway, leading to dynamic structural alterations in these proteins. Furthermore, supplementation with tryptophan was shown to significantly enhance mitochondrial function in oocytes, regulate the glutathione (GSH)/oxidized glutathione (GSSG) ratio, reduce reactive oxygen species (ROS) levels, and alleviate oxidative stress, thereby mitigating the decline in oocyte quality caused by PFOS exposure. These findings provide novel theoretical insights and research directions for using tryptophan as a protective agent against PFOS-induced reproductive toxicity.