Comparative cardiotoxicity assessment of bisphenol chemicals and estradiol using human induced pluripotent stem cell-derived cardiomyocytes

Authors

Blake L. Cooper, Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Hospital, Washington, District of Columbia 20010, USA.
Shatha Salameh, Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Hospital, Washington, District of Columbia 20010, USA.
Nikki Gillum Posnack, Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Hospital, Washington, District of Columbia 20010, USA.

Document Type

Journal Article

Publication Date

3-26-2024

Journal

Toxicological sciences : an official journal of the Society of Toxicology

Volume

198

Issue

2

DOI

10.1093/toxsci/kfae015

Keywords

bisphenol; calcium; cardiomyocyte; electrophysiology; estrogen

Abstract

Bisphenol A (BPA) is commonly used to manufacture consumer and medical-grade plastics. Due to health concerns, BPA substitutes are being incorporated-including bisphenol S (BPS) and bisphenol F (BPF)-without a comprehensive understanding of their toxicological profile. Previous studies suggest that bisphenol chemicals perturb cardiac electrophysiology in a manner that is similar to 17β-estradiol (E2). We aimed to compare the effects of E2 with BPA, BPF, and BPS using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). Cardiac parameters were evaluated using microelectrode array (MEA) technology and live-cell fluorescent imaging. Cardiac metrics remained relatively stable after exposure to nanomolar concentrations (1-1000 nM) of E2, BPA, BPF, or BPS. At higher micromolar concentrations, chemical exposures decreased the depolarization spike amplitude, and shortened the field potential, action potential duration, and calcium transient duration (E2 ≥ BPA ≥ BPF ≫ BPS). Cardiomyocyte physiology was largely undisturbed by BPS. BPA-induced effects were exaggerated when coadministered with an L-type calcium channel (LTCC) antagonist or E2, and reduced when coadministered with an LTCC agonist or an estrogen receptor alpha antagonist. E2-induced effects were not exaggerated by coadministration with an LTCC antagonist. Although the observed cardiac effects of E2 and BPA were similar, a few distinct differences suggest that these chemicals may act (in part) through different mechanisms. hiPSC-CM are a useful model for screening cardiotoxic chemicals, nevertheless, the described findings should be validated using a more complex ex vivo and/or in vivo model.

APA Citation

Cooper, Blake L.; Salameh, Shatha; and Posnack, Nikki Gillum, "Comparative cardiotoxicity assessment of bisphenol chemicals and estradiol using human induced pluripotent stem cell-derived cardiomyocytes" (2024). GW Authored Works. Paper 4481.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/4481

Department

Pediatrics