Bisphenol A impairs contractile function and vascular development in human cardiac organoids: Insights from toxicity assessment and risk evaluation

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 (hESCs) and exposed hCOs to BPA concentrations ranging from environmentally relevant to higher experimental levels (0.1–10 μmol/L) throughout differentiation. BPA exposure dose-dependently impaired cardiomyocyte contractility and disrupted endothelial network formation. 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. A potential molecular sensitivity point for vascular impairment was observed at 0.5 μmol/L BPA. 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.