Stage-specific cardiotoxicity induced by bisphenol A using human pluripotent stem cell-derived 2D- and 3D-cardiomyocyte models

초록

Bisphenol A (BPA), a widely used industrial chemical with endocrine-disrupting properties, raises developmental and cardiotoxicity concerns. We established a stage-specific cardiotoxicity platform using human pluripotent stem cell (hPSC)-derived cardiomyocytes in two-dimensional and three-dimensional (3D) cultures. BPA exposure at >= 10 mu M significantly reduced cell viability and downregulated pluripotency and cardiac lineage markers such as OCT4, NKX2-5, and cTnT in a stage-dependent manner. Electrophysiological analysis revealed that acute exposure to 10 mu M BPA disrupted action potentials in hPSC-derived cardiomyocytes, inducing membrane depolarization and rhythm disturbances. Furthermore, 3D cardiac tissues treated with 10 or 50 mu M BPA exhibited severe mitochondrial deformation and impaired contractile function, as observed by TEM and beating analysis. Reproducing these effects in a personalized hPSC line validated the platform's applicability for patient-specific toxicity assessment. These findings highlight the importance of integrating developmental stage-specific and 3D human-relevant models for comprehensive cardiotoxicity evaluation of environmental chemicals such as BPA.

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