The effects of trichloroethylene on cardiac differentiation in human embryonic stem cells and its mechanisms / 中国应用生理学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To explore the effects of trichloroethylene (TCE) on cardiac developmental differentiation in human embryonic stem cells.</p><p><b>METHODS</b>In this study, based on the human embryonic stem cells in vitro cardiac differentiation assay, we investigated the potential effect of TCE exposure on the cardiac toxicity in embryo development. Human embryonic stem cells were treated with TCE at different concentrations of 100 ppb, 1 ppm, and 10 ppm and dimethyl sulfoxide(DMSO) treated as control. The MTT assay was performed to examine the cytoplasmic toxicity of TCE exposure. The beating percentages were recorded and the expression of cardiac specific gene was evaluated by PCR or flow cytometry. Also, real time PCR was performed to verify the micro array analysis on the expression level changes of genes which were involved in the Ca2+ signal pathways.</p><p><b>RESULTS</b>Compared with the control group, there was no significant difference in cell viability when cells were treated with TCE at the concentrations of 100 ppb, 1 ppm, and 10 ppm. However, TCE could inhibit the expression of cTnT protein in a concentration-dependant manner. And the most interestingly, TCE significantly inhibited the cardiac differentiation characterized by the decrease beating percentages. Genes involved in Ca2+ signaling pathway were severely disrupted by TCE.</p><p><b>CONCLUSION</b>TCE inhibited the cardiac specific differentiation of human embryonic stem cell and at the meanwhile the genes responsible for Ca2+ signaling pathway were severely disrupted, which could contribute the severe effects of TCE cardiotoxicity.</p>