{"doi":"10.1101/2023.09.13.557564","title":"Comparative cardiotoxicity assessment of bisphenol chemicals and estradiol using human induced pluripotent stem cell-derived cardiomyocytes","abstract":"ABSTRACT Background 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. Objective 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). Methods Cardiac parameters were evaluated using microelectrode array (MEA) technology and live-cell fluorescent imaging at baseline and in response to chemical exposure (0.001-100 μM). Results Cardiac metrics remained relatively stable after exposure to nanomolar concentrations (1-1,000 nM) of E2, BPA, BPF, or BPS. At higher micromolar concentrations, chemical exposures resulted in a decrease in the depolarizing spike amplitude, shorter field potential and action potential duration, shorter calcium transient duration, and decrease in hiPSC-CM contractility (E2 > BPA > BPF >> BPS). Cardiomyocyte physiology was largely undisturbed by BPS exposure. BPA-induced effects were exaggerated when co-administered with an L-type calcium channel antagonist (verapamil) or E2 - and reduced when co-administered with an L-type calcium channel agonist (Bay K8644) or an estrogen receptor alpha antagonist (MPP). E2-induced effects generally mirrored those of BPA, but were not exaggerated by co-administration with an L-type calcium channel antagonist. Discussion Collectively across multiple cardiac endpoints, E2 was the most potent and BPS was the least potent disruptor of hiPSC-CM function. 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 in vitro findings should be validated using a more complex ex vivo and/or in vivo model.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":400767,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9608,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1056000,"name":"Shatha Salameh","orcid":"0000-0001-9624-4277","position":1,"is_corresponding":false},{"id":283026,"name":"Nikki Gillum Posnack","orcid":"0000-0002-3880-7200","position":2,"is_corresponding":false},{"id":283025,"name":"Blake Cooper","orcid":"0000-0001-8222-2560","position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-19T01:20:04.010538Z","pmid":"37745451","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}