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Updated: Jun 19, 2026
Nuclei Isolation from Mouse Cardiac Progenitor Cells for Epigenome and Gene Expression Profiling at Single-Cell Resolution
Published on: May 12, 2023
Gene expression profiling in the fetal cardiac tissue after folate and low-dose trichloroethylene exposure
Patricia T Caldwell1, Ann Manziello, Jamie Howard
1Department of Veterinary Science and Microbiology, University of Arizona, Tucson, Arizona 85721-0038, USA.
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.
Insights
Trichloroethylene (TCE) exposure alters embryonic heart gene expression, and folate supplementation does not protect against these effects. In fact, folate may be detrimental when combined with TCE exposure.
Area of Science:
- Developmental toxicology
- Molecular biology
- Cardiovascular research
Background:
- Trichloroethylene (TCE) exposure is linked to cardio-teratogenic effects in animal models.
- TCE may disrupt cardiac function by altering calcium homeostasis and interfering with the folic acid/methylation pathway.
- Epigenetic modifications are a potential mechanism for TCE-induced gene regulation changes.
Purpose of the Study:
- To investigate transcriptional targets affected by TCE in embryonic mouse hearts.
- To determine if maternal folate supplementation can counteract TCE's effects on embryonic heart gene expression.
Main Methods:
- Utilized DNA microarray technology to profile gene expression.
- Examined embryonic mouse hearts from mothers exposed to TCE and varying folate levels.
Main Results:
- Low-dose TCE exposure significantly altered transcripts involved in transport, ion channels, transcription, differentiation, cytoskeleton, cell cycle, and apoptosis.
- Folate supplementation did not mitigate TCE's impact on gene expression.
- Both high and low folate levels induced additional significant changes in gene expression.
Conclusions:
- TCE-induced folate deficiency does not explain altered gene expression in the embryonic heart.
- Folate supplementation may be harmful and not protective during TCE exposure in developing embryos.
