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.
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.
Authors: Alondra P Harris; Kareem A Ismail; Martha Nunez; Ira Martopullo; Alejandro Lencinas; Ornella I Selmin; Raymond B Runyan Journal: Toxicol Lett Date: 2018-01-04 Impact factor: 4.372
Authors: Sheri Chen; Alejandro Lencinas; Martha Nunez; Ornella I Selmin; Raymond B Runyan Journal: Environ Sci Process Impacts Date: 2020-03-11 Impact factor: 4.238
Authors: Lynn B Bailey; Patrick J Stover; Helene McNulty; Michael F Fenech; Jesse F Gregory; James L Mills; Christine M Pfeiffer; Zia Fazili; Mindy Zhang; Per M Ueland; Anne M Molloy; Marie A Caudill; Barry Shane; Robert J Berry; Regan L Bailey; Dorothy B Hausman; Ramkripa Raghavan; Daniel J Raiten Journal: J Nutr Date: 2015-06-03 Impact factor: 4.798
Authors: Weihsueh A Chiu; Jennifer Jinot; Cheryl Siegel Scott; Susan L Makris; Glinda S Cooper; Rebecca C Dzubow; Ambuja S Bale; Marina V Evans; Kathryn Z Guyton; Nagalakshmi Keshava; John C Lipscomb; Stanley Barone; John F Fox; Maureen R Gwinn; John Schaum; Jane C Caldwell Journal: Environ Health Perspect Date: 2012-12-18 Impact factor: 9.031