title: Gene expression profiling in the fetal cardiac tissue after folate and low-dose trichloroethylene exposure.
abstract: BACKGROUND
  Previous studies show gene expression alterations in rat embryo hearts and cell lines that correspond to the cardio-teratogenic effects of trichloroethylene (TCE) in animal models. One potential mechanism of TCE teratogenicity may be through altered regulation of calcium homeostatic genes with a corresponding inhibition of cardiac function. It has been suggested that TCE may interfere with the folic acid/methylation pathway in liver and kidney and alter gene regulation by epigenetic mechanisms. According to this hypothesis, folate supplementation in the maternal diet should counteract TCE effects on gene expression in the embryonic heart.
  
  
  METHODS
  To identify transcriptional targets altered in the embryonic heart after exposure to TCE, and possible protective effects of folate, we used DNA microarray technology to profile gene expression in embryonic mouse hearts with maternal TCE exposure and dietary changes in maternal folate.
  
  
  RESULTS
  Exposure to low doses of TCE (10 ppb) 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.
  
  
  CONCLUSIONS
  A mechanism by which TCE induces a folate deficiency does not explain altered gene expression patterns in the embryonic mouse heart. The data further suggest that use of folate supplementation, in the presence of this toxin, may be detrimental and not protective of the developing embryo.
authors.affiliation: Department of Veterinary Science and Microbiology, University of Arizona, Tucson, Arizona 85721-0038, USA.
authors.forename: Patricia T
authors.initials: PT
authors.lastname: Caldwell
authors.forename: Ann
authors.initials: A
authors.lastname: Manziello
authors.forename: Jamie
authors.initials: J
authors.lastname: Howard
authors.forename: Brittany
authors.initials: B
authors.lastname: Palbykin
authors.forename: Raymond B
authors.initials: RB
authors.lastname: Runyan
authors.forename: Ornella
authors.initials: O
authors.lastname: Selmin
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000235:genetics* / Q000517:prevention & control; D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D019587:Dietary Supplements / Q000009:adverse effects; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage; D005494:Folic Acid Deficiency / Q000139:chemically induced / Q000150:complications; D020869:Gene Expression Profiling; D006321:Heart / Q000187:drug effects* / Q000254:growth & development; D006330:Heart Defects, Congenital / Q000139:chemically induced* / Q000235:genetics / Q000517:prevention & control; D007473:Ion Channels / Q000187:drug effects / Q000235:genetics; D017136:Ion Transport / Q000187:drug effects / Q000235:genetics; D051379:Mice; D038081:Organogenesis / Q000187:drug effects / Q000235:genetics; D011247:Pregnancy; D051381:Rats; D013723:Teratogens / Q000633:toxicity*; D014241:Trichloroethylene / Q000037:antagonists & inhibitors / Q000633:toxicity*; D014874:Water Pollutants, Chemical / Q000037:antagonists & inhibitors / Q000633:toxicity*
chemical_list: D007473:Ion Channels; D013723:Teratogens; D014874:Water Pollutants, Chemical; D014241:Trichloroethylene; D005492:Folic Acid