Time-Dependent Effects of PFAS and Their Mixtures on Ovarian Epithelial Cell Proliferation and Chemotherapeutic Response

Per- and polyfluoroalkyl substances (PFAS) are an emerging group of anthropogenic environmental pollutants frequently detected in human and animal serum. Although several studies have reported adverse health effects associated with exposure to single PFAS, limited information is available concerning the biological and toxicological impact of PFAS mixtures and their potential interactions with chemotherapeutic agents. This study investigated the effects of acute and chronic exposure to PFAS, including perfluorooctanoic acid (PFOA, 3 nmol/L), perfluorooctane sulfonic acid (PFOS, 5 nmol/L), and their binary mixture containing 3 nmol/L of PFOA plus 5 nmol/L of PFOS, using an in vitro model, mouse ovarian surface epithelial cells (MOSEC), and possible interactions with antineoplastic agents. Results showed increased cell proliferation following acute PFOS exposure; this effect was enhanced in the PFOA-PFOS mixture. In contrast, PFOA exposure showed reduced cell proliferation. Acute exposure to PFOA, PFOS, and their mixture was associated with reduced sensitivity to cabazitaxel and docetaxel, while chronically exposed cells demonstrated increased sensitivity. These findings suggest that PFOA, PFOS, and their mixtures present in human serum and tissues may influence cellular proliferation and alter therapeutic response. These findings further highlight the importance of mixture effects and the exposure duration effect in the toxicological evaluation of PFAS toxicity.