2. Academic Validation
  3. Perfluorooctanoic acid exposure leads to defect in follicular development through disrupting the mitochondrial electron transport chain in granulosa cells

Perfluorooctanoic acid exposure leads to defect in follicular development through disrupting the mitochondrial electron transport chain in granulosa cells

  • Sci Total Environ. 2023 Sep 16;166954. doi: 10.1016/j.scitotenv.2023.166954.
Zhe Zhang 1,  Jiao Tian 2,  Wenwen Liu 2,  Jidong Zhou 2,  Yang Zhang 2,  Lijun Ding 2,  Haixiang Sun 3,  Guijun Yan 4,  Xiaoqiang Sheng 5
Affiliations

Affiliations

  • 1 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; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.
  • 2 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.
  • 3 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. Electronic address: [email protected].
  • 4 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. Electronic address: [email protected].
  • 5 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; Center for Reproductive Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. Electronic address: [email protected].
PMID: 37722425 DOI: 10.1016/j.scitotenv.2023.166954
Abstract

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.

Keywords

3D follicle culture; Granulosa cell; Mitochondrial dysfunction; Ovarian function; Perfluorooctanoic acid; Resveratrol.

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