Bisphenol A impairs contractile function and vascular development in human cardiac organoids:Insights from toxicity assessment and evidence-based risk evaluationOA

Bisphenol A(BPA),a widely encountered environmental endocrine-disrupting chemical,has been linked to an increased risk of congenital heart defects in epidemiological and experimental studies.To investigate its impact in a human-relevant system,we used a human cardiac organoid(hCO)model derived from human embryonic stem cells and exposed hCOs to BPA concentrations ranging from environmentally relevant to higher experimental levels(0.1–10μmol/L)throughout differentiation.BPA exposure impaired cardiac contractile function and disrupted endothelial network formation,with more pronounced functional effects at higher concentrations.BPA exposure also induced apoptosis in hCOs.Subsequently,transcriptomic profiling revealed dysregulation of genes associated with cardiac rhythm and developmental signaling in BPA-treated hCOs.Among the concentrations tested,0.5μmol/L was the lowest concentration associated with a significant reduction in CD31 fluorescence intensity.This research provides in vitro evidence that BPA can perturb key processes in early human heart development,highlighting the necessity for further mechanistic and in vivo studies to clarify exposure relevance and its potential implications for fetal heart health.