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Genes, folate and homocysteine in embryonic development

Published online by Cambridge University Press:  28 August 2007

Thomas H. Rosenquist  and
Richard H. Finnell
Thomas H. Rosenquist*
Affiliation:
Department of Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198–6395, USA
Richard H. Finnell
Affiliation:
Department of Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198–6395, USA Center for Human Molecular Genetics, University of Nebraska Medical Center, Omaha, NE 68198–6395, USA
*
*Corresponding author: Professor Thomas H. Rosenquist, fax +1 402 559 3990, email [email protected]
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Abstract

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Population-based studies of human pregnancies show that periconceptional folate supplementation has a significant protective effect for embryos during early development, resulting in a significant reduction in developmental defects of the face, the neural tube, and the cono-truncal region of the heart. These results have been supported by experiments with animal models. An obvious quality held in common by these three anatomical regions is that the normal development of each region depends on a set of multi-potent cells that originate in the mid-dorsal region of the neural epithelium. However, the reason for the sensitive dependence of these particular cells on folic acid for normal development has not been obvious, and there is no consensus about the biological basis of the dramatic rescue with periconceptional folate supplementation. There are two principal hypotheses for the impact of folate insufficiency on development; each of these hypotheses has a micronutrient component and a genetic component. In the first hypothesis the effect of low folate is direct, limiting the availability of folic acid to cells within the embryo itself; thus compromising normal function and limiting proliferation. The second hypothetical effect is indirect: low folate disrupts methionine metabolism; homocysteine increases in the maternal serum; homocysteine induces abnormal development by inhibiting the function of N-methyl-D-aspartate (NMDA) receptors in the neural epithelium. There are three general families of genes whose level of expression may need to be considered in the context of these two related hypotheses: folate-receptor genes; genes that regulate methionine– homocysteine metabolism; NMDA-receptor genes.

Keywords

GenesFolateHomocysteineEmbryonic developmental defects
Type
Micronutrient and Reprod. and Dev. Grps Sym. on relative contribution of diet and genotype to dev.
Information
Proceedings of the Nutrition Society , Volume 60 , Issue 1 , February 2001 , pp. 53 - 61
Copyright
Copyright © The Nutrition Society 2001

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