Mixed exposure to PFOA and PFOS induces oocyte apoptosis and subfertility in mice by activating the Hippo signaling pathway

Abstract

Per- and polyfluoroalkyl substances (PFAS) are synthetic perfluorinated compounds known for their persistence in the environment and reproduction toxicity. PFAS, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), have been identified in the follicular fluid of infertile women. However, the specific of PFOA and PFOS mixture on oocyte quality and female fertility remain unclear. In this study, we exposed female mice to combination of PFOA and PFOS to investigate the underlying mechanisms impairing fertility and oocyte maturation. Our results showed that exposure to the mixture induced epigenetic alterations and DNA damage in oocytes, impairing meiosis. Additionally, mitochondrial dysfunction caused by the exposure to the mixture led to oxidative stress and apoptosis in the oocytes. The reduction in oocyte quality resulted in a decrease in blastocyst quality and litter size. Furthermore, single-cell transcriptome analysis indicated that exposure to the mixture disrupted energy metabolism and triggered apoptosis, possibly through the activation of the Hippo signaling pathway. Overall, our results suggest that exposure to PFOA and PFOS mixture impairs the fertility in mice through the activation of the Hippo signaling pathway-induced oocytes apoptosis.