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(2019) Cardiogenesis impairment promoted by bisphenol A exposure is successfully counteracted by epigallocatechin gallate. Environmental pollution (Barking, Essex : 1987);;2019 Mar;246:1008-1019

Exposure to the emerging contaminant Bisphenol A (BPA) is ubiquitous and associated with cardiovascular disorders. BPA effect as endocrine disruptor is widely known but other mechanisms underlying heart disease, such as epigenetic modifications, remain still unclear. A compound of green tea, epigallocatechin gallate (EGCG), may act both as anti-estrogen and as inhibitor of some epigenetic enzymes. The aims of this study were to analyze the molecular processes related to BPA impairment of heart development and to prove the potential ability of EGCG to neutralize the toxic effects caused by BPA on cardiac health. Zebrafish embryos were exposed to 2000 and 4000a-I1/4g/L BPA and treated with 50 and 100a-I1/4M EGCG. Heart malformations were assessed at histological level and by confocal imaging. Expression of genes involved in cardiac development, estrogen receptors and epigenetic enzymes was analyzed by qPCR whereas epigenetic modifications were evaluated by whole mount immunostaining. BPA embryonic exposure led to changes in cardiac phenotype, induced an overexpression of hand2, a crucial factor for cardiomyocyte differentiation, increased the expression of estrogen receptor (esr2b), promoted an overexpression of a histone acetyltransferase (kat6a) and also caused an increase in histone acetylation, both mechanisms being able to act in sinergy. EGCG treatment neutralized all the molecular alterations caused by BPA, allowing the embryos to go on with a proper heart development. Both molecular mechanisms of BPA action (estrogenic and epigenetic) likely lying behind cardiogenesis impairment were successfully counteracted by EGCG treatment.

MEDLINE 31126002 : Cardiogenesis impairment promoted by bisphenol A exposure is successfully counteracted by epigallocatechin gallate.

This project is supported by the Canadian Institutes of Health Research (award #111062), Alberta Innovates - Health Solutions, and by The Metabolomics Innovation Centre (TMIC), a nationally-funded research and core facility that supports a wide range of cutting-edge metabolomic studies. TMIC is funded by Genome Alberta, Genome British Columbia, and Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $900 million in funding from the federal government.