Perfluorooctanoic acid inhibits the maturation rate of mouse oocytes cultured in vitro by triggering mitochondrial and <scp>DNA</scp> damage
Conghui Guo, Zhihong Zhao, Kun Zhao, Jianhao Huang, Linshu Ding, Xiaogang Huang, Meng Li, Li Li, Hengxi Wei, Shouquan Zhang
Abstract
BACKGROUND: Perfluorooctanoic acid (PFOA) is widely used in the manufacture of household and industrial products. It has certain toxicity and leaves many residues in the environment. Numerous studies have shown that PFOA exhibits endocrine disrupting properties and immunotoxicity and induces developmental defects. However, there is very little information regarding its toxicity on oocytes. METHODS: We cultured denuded oocytes in maturation medium supplemented with 0, 300, or 500 PFOA during IVM and evaluated the maturation of oocytes from the aspects of ROS(DCFH-DA), mitochondria(MitoOrange and JC-1), DNA damage(P-H2AX), and cytoskeleton(β-tubulin). RESULTS: Compared with the control group, the PFOA treatment group exhibited significantly reduced proportion of oocytes matutation. Furthermore, the DCFH-DA test showed that PFOA significantly increased reactive oxygen species (ROS) levels. PFOA disrupted mitochondrial distribution and decreased mitochondrial function as assessed using MitoOrange and JC-1. In addition, PFOA-treated oocytes exhibited a significantly higher percentage of P-H2AX, defective β-tubulin, abnormal chromosome alignment, lower expression of the anti-apoptotic gene Bcl-2, and higher expression of the apoptotic genes caspase3 and Bax. CONCLUSION: In summary, PFOA could negatively and directly affect oocyte maturation in vitro and cause oxidative stress, mitochondrial function disruption, DNA damage, cytoskeleton damage, and apoptosis.