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Final Progress Reports: University of Arizona: Susceptibility to Trichloroethylene (TCE) and Chlorinated Acids in Heart Development

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Superfund Research Program

Susceptibility to Trichloroethylene (TCE) and Chlorinated Acids in Heart Development

Project Leader: Ornella Selmin
Grant Number: P42ES004940
Funding Period: 2000-2010

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Final Progress Reports

Year:   2009  2004 

To identify transcriptional targets altered in the embryonic heart after exposure to TCE, as well as possible protective effects of folate, Dr. Selmin's team used DNA microarray technology in a model of maternal TCE exposure through drinking water and dietary changes in maternal folate. The researchers observed that both high and low folate in the maternal diet led to similar phenotypic outcomes in the embryos, and exposure to 10 ppb TCE counteracted the effects of high and low folate alone. In control dams, both at low and high folate, the researchers observed an increased rate of resorpted and developmentally delayed embryos and a decrease in normally developed embryos. However, in the TCE-exposed dams of the corresponding folate groups, the researchers observed an almost perfect inversion of phenotypic outcomes. Overall, these results suggest that TCE may facilitate the progression of embryos in low or high folate groups through otherwise restrictive developmental checkpoints.

Microarray data of the embryos indicate that exposure to low doses of TCE (10ppb) caused extensive alterations in transcripts encoding proteins involved in transport, ion channel, transcription, differentiation, cytoskeleton, cell cycle and apoptosis. Exogenous folate did not offset the effects of TCE exposure on normal gene expression, and both high and low levels of folate produced additional significant changes in gene expression. Taken together, the researchers' findings suggest that exogenous folate, whether to restore normal folate levels or raise endogenous levels, does not offset the effects of TCE exposure on altered gene expression. Thus, a mechanism where TCE produces a folate deficiency does not explain altered gene-expression patterns in the embryonic mouse heart. Additionally, the researchers' data support the notion that environmental concentrations of TCE caused drastic changes in gene expression during critical phases of heart development and that the optimal dose of folate intervention needs to be determined for safe and effective prenatal care.

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