Gene expression profiling in the fetal cardiac tissue after folate and low-dose trichloroethylene exposure

Patricia T. Caldwell, Ann Manziello, Jamie Howard, Brittany Palbykin, Raymond B Runyan, Ornella Selmin

Research output: Contribution to journalArticle

19 Citations (Scopus)

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. APPROACH: 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

Original languageEnglish (US)
Pages (from-to)111-127
Number of pages17
JournalBirth Defects Research Part A - Clinical and Molecular Teratology
Volume88
Issue number2
DOIs
StatePublished - Feb 2010

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Trichloroethylene
Gene Expression Profiling
Folic Acid
Fetus
Gene Expression
Embryonic Structures
Mothers
Maternal Exposure
Oligonucleotide Array Sequence Analysis
Cytoskeleton
Ion Channels
Transcriptome
Epigenomics
Methylation
Genes
Cell Cycle
Animal Models
Apoptosis
Diet
Calcium

Keywords

  • Cardiac
  • Embryonic development
  • Folate
  • Gene expression
  • Halogenated hydrocarbons
  • Ryanodine receptor
  • Trichloroethylene

ASJC Scopus subject areas

  • Developmental Biology
  • Pediatrics, Perinatology, and Child Health
  • Embryology

Cite this

Gene expression profiling in the fetal cardiac tissue after folate and low-dose trichloroethylene exposure. / Caldwell, Patricia T.; Manziello, Ann; Howard, Jamie; Palbykin, Brittany; Runyan, Raymond B; Selmin, Ornella.

In: Birth Defects Research Part A - Clinical and Molecular Teratology, Vol. 88, No. 2, 02.2010, p. 111-127.

Research output: Contribution to journalArticle

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