Environmentally relevant concentrations of individual per- and polyfluoroalkyl substances (PFAS) and a PFAS mixture impact proliferation, migration, and gene transcription in a human myometrial cell line

Abstract

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants linked to adverse health effects. Epidemiological studies have linked PFAS with an increased risk of uterine diseases including fibroids however, the mechanisms involved remain to be elucidated. This study examined the impact of individual PFAS, such as legacy compounds [perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS)] and alternative short-chain compounds [GENX/HFPO-DA and perfluorobutanesulfonic acid (PFBS)], along with a PFAS mixture, on the function and transcriptome of immortalized human myometrial cells (UT-TERT). Exposure to these PFAS resulted in increased cell viability and proliferation. Flow cytometry showed that PFOS and the PFAS mixture altered cell cycle progression, while migration assays indicated significant enhancement of cell migration following PFOS and mixture exposure. Moreover, PFOA, PFBS, and the PFAS mixture impaired gap junction intercellular communication (GJIC), suggesting possible disruptions in cellular communication in the uterine environment. Transcriptomic analysis identified extensive changes in gene expression after exposure to environmentally relevant PFAS levels, revealing common molecular pathways involved in cell signaling, lipid metabolism, and cell survival. These findings provide crucial insights into how PFAS may contribute to reproductive health risks, warranting further investigation into the long-term effects of PFAS on uterine function and overall reproductive health.