Folate protection from congenital heart defects linked with canonical Wnt signaling and epigenetics

PURPOSE OF REVIEW: Environmental factors, such as drugs, chemicals, or abnormal concentrations of natural metabolites, induce birth defects. Environmental effects on cardiogenesis have been little studied in contrast to neurogenesis. This review presents evidence on three environmental factors: alcohol, the drug lithium, and the metabolite homocysteine, impacting the Wnt/β-catenin pathway during cardiac development and folate protection. RECENT FINDINGS: Animal and epidemiological studies have shown that folate protects the embryo from birth defects. New animal studies demonstrate that folate prevents cardiovascular defects induced by the drug lithium, homocysteine, or alcohol, but protection occurs at a higher concentration than currently used in vitamin supplements. The data indicate that folate in combination with myo-inositol may further reduce the risk of birth defects. Discussion is presented of the cell specification stages that are impacted resulting in cardiac defects, how Wnt/β-catenin signaling is involved, and how folate and myo-inositol additively may protect embryonic pathways. The possible epigenetic role of folate in Wnt/β-catenin signaling is described. SUMMARY: This review will enable better counseling of women by defining, during early pregnancy, a susceptible window of embryonic exposure leading to a high risk of cardiac defects, and provides a therapeutic means and the necessary timing for prevention of environmentally induced birth defects.