PFOS exposure impairs porcine oocyte maturation and embryo development via mitochondria-dependent ferroptosis

Perfluorooctane sulfonate (PFOS) is a widely utilized chemical known for its exceptional environmental stability over extended periods, its significant potential to bioaccumulate in living organisms, and its considerable risks to both health and the environment. Several studies have suggested that PFOS may pose reproductive risks in mammals; however, the exact mechanisms driving these effects are not well understood. In this study, we explored the possible mechanisms by which PFOS toxicity affects the maturation of mammalian oocytes and the embryonic development employing porcine oocytes as a model system. SMART-seq results suggested that PFOS may affect oocyte maturation through mechanisms involving ferroptosis, autophagy, and alterations in membrane structure. Our results suggest that PFOS exposure adversely affects mitochondrial function and structure, thereby influencing peroxisome biogenesis and contributing to oxidative stress. Most importantly, we found that exposure to PFOS significantly elevated Fe²⁺ levels, an indicator associated with ferroptosis in oocytes. Furthermore, malondialdehyde (MDA) levels in the PFOS group were significantly higher than those in the control group. Additionally, the mRNA expression levels of PCBP1 and PCBP2, which are related to ferroptosis, as well as the expression level of P53, were significantly reduced in the PFOS group. Overall, exposure to PFOS in vitro results in mitochondrial damage in porcine oocytes, which induces lipid peroxidation and subsequently leads to the occurrence of ferroptosis.