Developmental effects of PFOS, PFOA and GenX in a 3D human induced pluripotent stem cell differentiation model

Polyfluoroalkyl substances (PFASs), including perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic (PFOA), are persistent pollutants routinely found in human blood. PFASs have been associated with health issues such as decreased birth weight impaired vaccination response children. Substitutes to these PFASs, ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)propanoate (GenX) introduced, although hazard information is limited. Human induced pluripotent stem cell (hiPSC) based models valuable for studying compounds, they mimic embryonic development. We used our recently developed PluriBeat assay investigate PFOS, PFOA GenX effects on early development vitro. In hiPSCs go through the stages of 3D cultures embryoid bodies (EBs) that blastocyst until finally form beating cardiomyocytes. Both PFOS had a strong effect cardiomyocyte differentiation at non-cytotoxic concentrations, being more potent than PFOA. Moreover, both compounds EB size highest test concentrations. weak concentration-dependent one hiPSC line, but not another. Transcriptional analysis mRNA from cardiomyocytes showed increased expression cardiac marker ISL1, whereas MYH7. This suggest perturb by disrupting molecular pathways similar those taking place developing embryo. Based findings, we conclude has potential become valuable, sensitive model system elucidating embryotoxic future.