Grant: Project Grant

Folate and choline are important nutrients required to support healthy pregnancies. Inadequate intake of these nutrients before and during pregnancy can increase the risk of birth defects and other pregnancy complications. Folate is a critical vitamin that provides the building blocks for DNA (e.g. purines) and methyl groups for a host of biosynthetic reactions. Choline is required to produce important components of cell membranes, and the neurotransmitter acetylcholine. Choline becomes even more important when folate metabolism is disturbed, because it replaces folate for certain functions. Although most Canadian women are aware of the importance of folate and reach the recommended intakes due to folate fortification programs and use of folate supplements, 85-90% do not have adequate choline intakes. Gene variants in folate metabolism, such as MTHFD1 R653Q, may also increase risk for neural tube defects, heart defects and other pregnancy complications. About 20% of Canadians have the QQ genotype, which we have shown to impair MTHFD1 function and decrease purine synthesis. Some studies have suggested that QQ women are more sensitive to low choline intake. Our goal is to determine whether inadequate choline contributes to the reproductive complications associated with the 653QQ genotype, and whether supplementation with choline or choline metabolites can overcome the effect of the genetic defect. We will examine human placentas from women with the 653RR and QQ genotypes with high and low folate intakes to assess the effects of diet and genotype on choline metabolism. We will use our mouse model for the variant to determine if low choline diets impair embryonic development and see if different types of choline supplements improve pregnancy outcomes. Our research will highlight a neglected aspect of nutrition during pregnancy and lay the groundwork for personalized dietary recommendations based on R653Q genotype to prevent reproductive complications.