Trichloroethylene Inhibits Development of Embryonic Heart Valve Precursors in Vitro

• Published in: Toxicological sciences 2000-01, Vol.53 (1), p.109-117
• Main Authors: Boyer, Angelique S., Finch, Wendy T., Runyan, Raymond B.
• Format: Article
• Language: English
• Subjects: Actins - metabolism; Alcohol Oxidoreductases - metabolism; Animals; Biological and medical sciences; cardiac valve formation; cardiogenesis; Cell Count; Cell Differentiation - drug effects; Cell Movement - drug effects; Cells, Cultured; Chick Embryo; Dose-Response Relationship, Drug; Embryology: invertebrates and vertebrates. Teratology; Endocardial Cushion Defects - chemically induced; Endocardial Cushion Defects - metabolism; Endothelium - cytology; Endothelium - drug effects; Endothelium - metabolism; Epithelial Cells - cytology; Epithelial Cells - drug effects; Epithelial Cells - metabolism; epithelial-mesenchymal cell transformation; Fibrillin-2; Fibrillins; Fluorescent Antibody Technique, Indirect; Fundamental and applied biological sciences. Psychology; Heart Valves - drug effects; Heart Valves - embryology; Heart Valves - metabolism; Mesoderm - cytology; Mesoderm - drug effects; Mesoderm - metabolism; Microfilament Proteins - metabolism; Mox-1; TCE; Teratology. Teratogens; Trichloroethylene - toxicity
• ISSN: 1096-6080; 1096-0929; 1096-0929
• DOI: 10.1093/toxsci/53.1.109

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 α-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.