{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T19:45:11Z","timestamp":1790106311637,"version":"4.0.1"},"reference-count":35,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2015,4,6]],"date-time":"2015-04-06T00:00:00Z","timestamp":1428278400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Nature Sciences Foundation of China","doi-asserted-by":"crossref","award":["81300143"],"award-info":[{"award-number":["81300143"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Postdoc Foundation of China","award":["2013M541718."],"award-info":[{"award-number":["2013M541718."]}]},{"name":"The Priority Academic Program Development of Jiangsu Higher Education Institutions."}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Trichloroethylene (TCE) is ubiquitous in our living environment, and prenatal exposure to TCE is reported to cause congenital heart disease in humans. Although multiple studies have been performed using animal models, they have limited value in predicting effects on humans due to the unknown species\u2010specific toxicological effects. To test whether exposure to low doses of TCE induces developmental toxicity in humans, we investigated the effect of TCE on human embryonic stem cells (hESCs) and cardiomyocytes (derived from the hESCs). In the current study, hESCs cardiac differentiation was achieved by using differentiation medium consisting of StemPro\u201034. We examined the effects of TCE on cell viability by cell growth assay and cardiac inhibition by analysis of spontaneously beating cluster. The expression levels of genes associated with cardiac differentiation and Ca<jats:sup>2+<\/jats:sup> channel pathways were measured by immunofluorescence and qPCR. The overall data indicated the following: (1) significant cardiac inhibition, which was characterized by decreased beating clusters and beating rates, following treatment with low doses of TCE; (2) significant up\u2010regulation of the <jats:italic>Nkx2.5\/Hand1<\/jats:italic> gene in cardiac progenitors and down regulation of the <jats:italic>Mhc\u20107\/cTnT<\/jats:italic> gene in cardiac cells; and (3) significant interference with Ca<jats:sup>2+<\/jats:sup> channel pathways in cardiomyocytes, which contributes to the adverse effect of TCE on cardiac differentiation during early embryo development. Our results confirmed the involvement of Ca<jats:sup>2+<\/jats:sup> turnover network in TCE cardiotoxicity as reported in animal models, while the inhibition effect of TCE on the transition of cardiac progenitors to cardiomyocytes is unique to hESCs, indicating a species\u2010specific effect of TCE on heart development. This study provides new insight into TCE biology in humans, which may help explain the development of congenital heart defects after TCE exposure. \u00a9 2015 Wiley Periodicals, Inc. 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