A Human-Induced Pluripotent Stem Cell-Derived Cardiomyocyte Platform for Environmental Cardiotoxicity Screening: Methodological Insights from Homosalate and Triphenyl Phosphate

Abstract

Introduction:

Environmental endocrine-disrupting chemicals (EDCs) are increasingly implicated as modifiable risk factors for cardiovascular disease (CVD) and yet their direct impact on human cardiac tissue remains poorly characterized. This study investigated the early transcriptional responses of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) following exposure to two structurally distinct and widely prevalent EDCs: homosalate (HS) and triphenyl phosphate (TPP).

Materials and Methods:

hiPSC-CMs were treated with 10, 30 or 60 µM of HS or TPP for 24 hours. Expression levels of key sarcomeric genes including MYL2, MYH7, TNNT2 and ACTN2 were quantified by RT-qPCR.

Results:

Both chemicals elicited dose-dependent repression of core contractile transcripts. TPP induced monotonic downregulation beginning at the lowest concentration tested while HS exhibited a biphasic response with mild gene induction at 10 µM and significant suppression at higher doses. Among all targets, MYL2 and MYH7 consistently emerged as the most transcriptionally sensitive markers.

Discussion:

These results highlight the sensitivity of sarcomeric gene expression to chemical exposure and suggest MYL2 and MYH7 as potential early indicators of chemically induced cardiac stress.

Conclusion:

This study underlines the responsiveness of the human cardiac transcriptome to environmental toxicants and supports the application of hiPSC-CMs as a human-relevant platform for mechanistic toxicology and early cardiotoxicity screening.