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Updated: Sep 28, 2026
Isolation and Culture of Avian Embryonic Valvular Progenitor Cells
Published on: October 28, 2010
Trichloroethylene inhibits development of embryonic heart valve precursors in vitro
A S Boyer1, W T Finch, R B Runyan
1Department of Cell Biology and Anatomy, University of Arizona, Tucson 85724, USA.
Abstract:
Previous epidemiological studies with humans and laboratory studies with chickens and rats linked trichloroethylene (TCE) exposure to cardiac defects. Although the cardiac defects in humans and laboratory animals produced by TCE are diverse, a majority of them involves valvular and septal structures. Progenitors of the valves and septa are formed by an epithelial-mesenchymal cell transformation of endothelial cells in the atrioventricular (AV) canal and outflow tract areas of the heart. Based on these studies, we hypothesized that TCE might cause cardiac valve and septa defects by specifically perturbing epithelial-mesenchymal cell transformation. We tested this hypothesis using an in vitro chick-AV canal culture model. This study shows that TCE affected several elements of epithelial-mesenchymal cell transformation. In particular, TCE blocked the endothelial cell-cell separation process that is associated with endothelial activation. Moreover, TCE inhibited mesenchymal cell formation throughout the concentration range tested (50-250 ppm). In contrast, TCE had no effect on the cell migration rate of the fully formed mesenchymal cells. Finally, the expression of 3 proteins (selected as molecular markers of epithelial-mesenchymal cell transformation) was analyzed in untreated and TCE-treated cultures. TCE inhibited the expression of the transcription factor Mox-1 and extracellular matrix (ECM) protein fibrillin 2. In contrast, TCE had no effect on the expression of alpha-smooth muscle actin. These data suggest that TCE may cause cardiac valvular and septal malformations by inhibiting endothelial separation and early events of mesenchymal cell formation in the heart.
Insights
Trichloroethylene (TCE) exposure may cause heart defects by disrupting a key cell process. This study found TCE inhibits endothelial cell separation and mesenchymal cell formation, crucial for heart valve and septum development.
Area of Science:
- Developmental biology
- Toxicology
- Cardiovascular research
Background:
- Epidemiological and laboratory studies link trichloroethylene (TCE) exposure to cardiac defects, particularly involving valvular and septal structures.
- Cardiac valve and septa formation relies on epithelial-mesenchymal cell transformation (EMT) of endothelial cells in the atrioventricular canal and outflow tract.
Purpose of the Study:
- To investigate the hypothesis that TCE specifically perturbs the EMT process, leading to cardiac defects.
- To elucidate the molecular mechanisms by which TCE may induce valvular and septal malformations.
Main Methods:
- Utilized an in vitro chick-atrioventricular (AV) canal culture model to assess TCE's effects on EMT.
- Quantified TCE's impact on endothelial cell-cell separation, mesenchymal cell formation, and migration.
- Analyzed the expression of key protein markers (Mox-1, fibrillin 2, alpha-smooth muscle actin) of EMT in TCE-exposed cultures.
Main Results:
- TCE exposure inhibited endothelial cell-cell separation, a process linked to endothelial activation.
- TCE significantly inhibited mesenchymal cell formation across tested concentrations (50-250 ppm).
- TCE reduced the expression of transcription factor Mox-1 and extracellular matrix protein fibrillin 2, but not alpha-smooth muscle actin.
Conclusions:
- TCE interferes with critical early stages of epithelial-mesenchymal cell transformation required for heart development.
- The findings suggest TCE may cause cardiac valvular and septal malformations by inhibiting endothelial separation and mesenchymal cell formation.
- This study provides mechanistic insights into TCE-induced cardiotoxicity at the cellular level.
