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

Per- and polyfluoroalkyl substances (PFAS) are environmental contaminants of concern due to their persistence and potential 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 investigated the effects of individual PFAS, including long-chain “legacy” PFAS [perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS)] and short-chain “alternative” PFAS compounds [undecafluoro-2-methyl-3-oxahexanoic acid (GENX/HFPO-DA), perfluorobutanesulfonic acid (PFBS)], as well as a mixture of these chemicals on the function and transcriptome of an immortalized human myometrial cell line (UT-TERT). UT-TERT cells exposed to individual PFAS displayed increased cell viability and proliferation. Flow cytometry analysis revealed that PFOS and the PFAS mixture altered cell cycle progression. Migration assays demonstrated that PFOS and the PFAS mixture significantly enhanced UT-TERT cell migration. Gap junction intercellular communication (GJIC) was impaired following PFOA, PFBS, and PFAS mixture exposure, indicating potential disruptions in cell-to-cell communication within the uterine environment. Transcriptomic analysis using RNA-seq identified substantial changes in gene expression after exposure to environmentally relevant levels of individual PFAS and PFAS mixture. Pathway analysis revealed common molecular pathways associated with PFAS exposure, including Cell-to-Cell Signaling, Lipid Metabolism, and Cell Death and Survival, while other pathways were unique to specific PFAS. These findings highlight the multifaceted effects of PFAS on myometrial cells, providing insights into the potential mechanisms underlying PFAS-associated health risks. Further research is necessary to elucidate the long-term implications of PFAS exposure on uterine function and overall reproductive health.