title: Disruption of cardiogenesis in human embryonic stem cells exposed to trichloroethylene.
abstract: 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-specific 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-34. 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 Ca2+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-regulation of the Nkx2.5/Hand1 gene in cardiac progenitors and down regulation of the Mhc-7/cTnT gene in cardiac cells; and (3) significant interference with Ca2+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 Ca2+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-specific 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. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1372-1380, 2016.
authors.affiliation: Department of Physiology and Neurobiology, Medical College, Soochow University, Suzhou, 215123, People's Republic of China.|Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, 215123, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Physiology and Neurobiology, Medical College, Soochow University, Suzhou, 215123, People's Republic of China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Physiology and Neurobiology, Medical College, Soochow University, Suzhou, 215123, People's Republic of China.
authors.forename: Guoxing
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Neurobiology, Medical College, Soochow University, Suzhou, 215123, People's Republic of China.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, 215123, People's Republic of China. tongjian@suda.edu.cn.|Department of Toxicology, Medical College, Soochow University, Suzhou, 215123, People's Republic of China. tongjian@suda.edu.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Tong
authors.affiliation: Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, 215123, People's Republic of China. tchen@suda.edu.cn.|Department of Toxicology, Medical College, Soochow University, Suzhou, 215123, People's Republic of China. tchen@suda.edu.cn.
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D024722:Cardiac Myosins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D000072576:Homeobox Protein Nkx-2.5 / Q000235:genetics / Q000378:metabolism; D000066449:Human Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D014241:Trichloroethylene / Q000633:toxicity*; D020107:Troponin T / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D024722:Cardiac Myosins; D000072576:Homeobox Protein Nkx-2.5; D018995:Myosin Heavy Chains; D014241:Trichloroethylene; D020107:Troponin T; C501641:MYH7 protein, human; C095552:NKX2-5 protein, human; C097341:helix-loop-helix protein, eHAND
keywords: cardiac differentiation; cardiac toxicity; gene expression; human embryonic stem cells (hESCs); trichloroethylene (TCE)