Yan Xiang-Zhu, Peng Jia, Liu Yu-Qing, Fan Ruo-Nan, Ni Xin-Yi, Gong Ling, Zhang Dan-Ni, Huang Xin, Tan Shu-Hua, Wang Hai-Long
College of Life Science, Hunan University of Science and Technology, Xiangtan, Hunan 411201, China; Department of Basic Medicine, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China.
Department of Basic Medicine, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China.
Reprod Toxicol. 2025 Mar;132:108829. doi: 10.1016/j.reprotox.2024.108829. Epub 2024 Dec 31.
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.
全氟和多氟烷基物质（PFAS）是一类合成的全氟化合物，以其在环境中的持久性和生殖毒性而闻名。PFAS、全氟辛酸（PFOA）和全氟辛烷磺酸（PFOS）已在不孕女性的卵泡液中被检测到。然而，PFOA和PFOS混合物对卵母细胞质量和女性生育能力的具体影响仍不清楚。在本研究中，我们将雌性小鼠暴露于PFOA和PFOS的混合物中，以研究损害生育能力和卵母细胞成熟的潜在机制。我们的结果表明，暴露于该混合物会诱导卵母细胞发生表观遗传改变和DNA损伤，从而损害减数分裂。此外，暴露于该混合物导致的线粒体功能障碍会导致卵母细胞中的氧化应激和细胞凋亡。卵母细胞质量的下降导致囊胚质量和产仔数减少。此外，单细胞转录组分析表明，暴露于该混合物会破坏能量代谢并引发细胞凋亡，可能是通过激活Hippo信号通路实现的。总体而言，我们的结果表明，暴露于PFOA和PFOS混合物会通过激活Hippo信号通路诱导卵母细胞凋亡，从而损害小鼠的生育能力。
