Perfluorooctanoic acid promotes proliferation of the human granulosa cell line HGrC1 and alters expression of cell cycle genes and Hippo pathway effector YAP1

Abstract

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.

Keywords: Granulosa cell; HGrC1 cells; Hippo pathway; Perfluorooctanoic acid; Reproductive toxicity; YAP1.