Related Experiment Video
Updated: Apr 15, 2026
Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation
Published on: June 17, 2015
Disruption of cardiogenesis in human embryonic stem cells exposed to trichloroethylene
Yan Jiang1,2, Dan Wang1, Guoxing Zhang1
1Department of Physiology and Neurobiology, Medical College, Soochow University, Suzhou, 215123, People's Republic of China.
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.
Insights
Prenatal exposure to trichloroethylene (TCE) can cause congenital heart defects. This study shows low-dose TCE inhibits human embryonic stem cell (hESC) cardiac differentiation, impacting Ca2+ pathways and revealing species-specific effects on heart development.
Area of Science:
- Toxicology
- Developmental Biology
- Cardiovascular Research
Background:
- Trichloroethylene (TCE) is a common environmental contaminant linked to congenital heart disease.
- Animal models have limitations in predicting TCE's effects on human heart development due to species-specific toxicology.
- Understanding TCE's impact on human embryonic development is crucial for assessing risks.
Purpose of the Study:
- To investigate the developmental toxicity of low-dose TCE exposure on human embryonic stem cells (hESCs) and their derived cardiomyocytes.
- To elucidate the mechanisms underlying TCE-induced cardiotoxicity in a human model.
- To identify species-specific effects of TCE on cardiac differentiation.
Main Methods:
- Utilized hESCs and differentiated them into cardiomyocytes using StemPro-34 medium.
- Assessed TCE effects on cell viability via cell growth assays.
- Quantified cardiac inhibition by analyzing spontaneously beating clusters and rates.
- Measured gene expression (Nkx2.5/Hand1, Mhc-7/cTnT) using immunofluorescence and qPCR.
- Examined interference with Ca2+ channel pathways in cardiomyocytes.
Main Results:
- Low-dose TCE significantly inhibited cardiac differentiation, reducing beating clusters and rates.
- TCE exposure led to up-regulation of Nkx2.5/Hand1 in cardiac progenitors and down-regulation of Mhc-7/cTnT in cardiomyocytes.
- Significant interference with Ca2+ channel pathways was observed in cardiomyocytes.
- The inhibitory effect on cardiac progenitor transition to cardiomyocytes was unique to hESCs.
Conclusions:
- TCE exposure at low doses induces cardiotoxicity in human embryonic stem cells.
- The Ca2+ turnover network is implicated in TCE-induced cardiotoxicity, consistent with animal studies.
- TCE's inhibitory effect on cardiac differentiation exhibits species-specific characteristics in humans.
- This study provides critical insights into TCE's mechanism of teratogenicity, potentially explaining congenital heart defects.
Related Concept Videos
00:57Embryonic Stem Cells
ES cells are grown in a culture medium where they can divide indefinitely, creating ES cell lines. Under certain conditions, ES cells can differentiate, either spontaneously into a variety of...
00:58Embryonic Stem Cells