Low Dose Pfda Induces DNA Damage and DNA Repair Inhibition by Promoting Nuclear Cgas Accumulation in Ovarian Epithelial Cells

Abstract

Per- and polyfluoroalkyl substances (PFAS), the versatile anthropogenic chemicals, are popular with the markets and manufactured in large quantities yearly. Accumulation of PFAS has various adverse health effects on human. Albeit certain members of PFAS were found to have genotoxicity in previous studies, the mechanisms of their effects on DNA damage repair (DDR) are still unknown. Here, we investigated the effects of Perfluorononanoic acid (PFDA) on DNA damage and DNA damage repair in ovarian epithelial cells through a series of in vivo and in vitro experiments. At environmentally relevant concentration, we firstly found that PFDA can cause DNA damage and induce nuclear cGAS increasing in primary mouse ovarian epithelial cells and IOSE-80 cells, which reduced the efficiency of DNA homologous recombination (HR) and perpetuated DNA double-strand breaks. Moreover, in vivo experiments also verified that PFDA can induce more DSBs lesions and nuclear cGAS in ovarian tissue. Taken together, our results unveiled that low dose PFDA can cause deleterious effects on DNA and DDR in ovarian epithelial cells and induce genomic instability.

Keywords: PFDA, DNA damage, cGAS, homologous recombination (HR), ovarian epithelial cells