Department of Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China; Center for Molecular Reproductive Medicine, Nanjing University, Nanjing, China.
Department of Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China; Center for Molecular Reproductive Medicine, Nanjing University, Nanjing, China.
Sci Total Environ. 2023 Dec 20;905:166954. doi: 10.1016/j.scitotenv.2023.166954. Epub 2023 Sep 16.
Perfluorooctanoic acid (PFOA) is a persistent environmental pollutant that can impair ovarian function, while the underlying mechanism is not fully understood, and effective treatments are lacking. In this study, we established a mouse model of PFOA exposure induced by drinking water and found that PFOA exposure impaired follicle development, increased apoptosis of granulosa cells (GCs), and hindered normal follicular development in a 3D culture system. RNA-seq analysis revealed that PFOA disrupted oxidative phosphorylation in ovaries by impairing the mitochondrial electron transport chain. This resulted in reduced mitochondrial membrane potential and increased mitochondrial reactive oxygen species (mtROS) in isolated GCs or KGN cells. Resveratrol, a mitochondrial nutrient supplement, could improve mitochondrial function and restore normal follicular development by activating FoxO1 through SIRT1/PI3K-AKT pathway. Our results indicate that PFOA exposure impairs mitochondrial function in GCs and affects follicle development. Resveratrol can be a potential therapeutic agent for PFOA-induced ovarian dysfunction.
全氟辛酸（PFOA）是一种持久性环境污染物，可损害卵巢功能，但其潜在机制尚不完全清楚，且缺乏有效的治疗方法。在本研究中，我们建立了饮水暴露于 PFOA 的小鼠模型，发现 PFOA 暴露可损害卵泡发育，增加颗粒细胞（GCs）的凋亡，并在 3D 培养系统中阻碍正常卵泡发育。RNA-seq 分析显示，PFOA 通过损害线粒体电子传递链来破坏卵巢中的氧化磷酸化。这导致分离的 GCs 或 KGN 细胞中线粒体膜电位降低和线粒体活性氧（mtROS）增加。白藜芦醇是一种线粒体营养补充剂，可通过 SIRT1/PI3K-AKT 通路激活 FoxO1 来改善线粒体功能并恢复正常的卵泡发育。我们的结果表明，PFOA 暴露可损害 GCs 中的线粒体功能并影响卵泡发育。白藜芦醇可能是 PFOA 诱导的卵巢功能障碍的潜在治疗剂。
