Olson Center for Women's Health, Department of Obstetrics and Gynecology, University of Nebraska Medical Center, Omaha, NE 68198, USA; Veterans Affairs Nebraska Western Iowa Health Care System, 4101 Woolworth Ave, Omaha, NE 68105, USA.
Key Lab of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science & Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
Reprod Toxicol. 2022 Jun;110:49-59. doi: 10.1016/j.reprotox.2022.03.011. Epub 2022 Mar 25.
Perfluorooctanoic acid (PFOA) is a common environmental contaminant that belongs to a group of manmade fluorinated chemicals called per- and polyfluoroalkyl substances (PFAS). Due to the pervasive nature of PFOA, the environmental health risks of PFOA contamination and exposure on reproductive health have increasing concern. In the present study, we exposed HGrC1 cells, an immortalized human granulosa cell line, to environmentally relevant (1-10 μM) concentrations of PFOA. Results indicated that HGrC1 cells treated with PFOA had increased proliferation and migration relative to vehicle treated controls. No differences in cell apoptosis were observed with 1-10 μM PFOA. Gene expression analysis revealed increases in mRNA transcripts for cell cycle regulators CCND1, CCNA2, and CCNB1. Upregulation of YAP1 protein and downstream target CTGF protein was also observed, suggesting that the Hippo pathway is involved in the proliferation and migratory effects of PFOA on HGrC1 cells. Further, the YAP1 inhibitor Verteporfin prevented the stimulatory effects of PFOA on HGrC1 cells. Together, these findings support a role for the Hippo pathway effector YAP1 in response to PFOA exposure in human granulosa cells.
全氟辛酸（PFOA）是一种常见的环境污染物，属于一类被称为全氟和多氟烷基物质（PFAS）的人造含氟化学品。由于 PFOA 的普遍存在，PFOA 污染和暴露对生殖健康的环境健康风险引起了越来越多的关注。在本研究中，我们将环境相关浓度（1-10 μM）的 PFOA 暴露于永生化人颗粒细胞系 HGrC1 细胞中。结果表明，与载体处理对照相比，用 PFOA 处理的 HGrC1 细胞增殖和迁移增加。用 1-10 μM PFOA 处理未观察到细胞凋亡的差异。基因表达分析显示细胞周期调节剂 CCND1、CCNA2 和 CCNB1 的 mRNA 转录物增加。还观察到 YAP1 蛋白和下游靶基因 CTGF 蛋白的上调，表明 Hippo 途径参与了 PFOA 对 HGrC1 细胞增殖和迁移的影响。此外，YAP1 抑制剂 Verteporfin 可阻止 PFOA 对 HGrC1 细胞的刺激作用。总之，这些发现支持 Hippo 途径效应物 YAP1 在人颗粒细胞对 PFOA 暴露的反应中的作用。
