Importance of folate-homocysteine homeostasis during early embryonic development

Shveta Taparia, Janée Gelineau-Van Waes, Thomas H. Rosenquist, Richard H. Finnell

Research output: Contribution to journalArticlepeer-review

61 Scopus citations


Although the beneficial effects of maternal folate supplementation in the periconceptional period have been shown to prevent neural tube defects, congenital heart defects and orofacial clefts, the exact protective mechanism of folates remains unknown. Folates affect DNA synthesis, amino acid metabolism and methylation of genes, proteins and lipids via S-adenosylmethionine-mediated one-carbon transfer reactions. Our laboratory has created several mouse knock out models of folate transport using gene targeting to inactivate folate receptor 1 (Folr1), folate receptor 2 (Folr2) and reduced folate carrier 1 (Slc19a1) genes. Gene ablation of both Folr1 and Slc19a1 leads to lethality, but with maternal folate supplementation, nullizygous embryos for both genes present with neural tube defects (NTDs) and congenital heart defects (CHDs). Folr1 nullizygous mice also exhibit orofacial clefts when the dams are provided with low folate supplementation during pregnancy. Finally, women with NTD-affected pregnancies have been reported to have high autoantibody titers against the folate receptor, potentially inhibiting the transport of folate to the developing embryo. This may be an explanation for some of the folate-responsive NTDs and perhaps other congenital malformations. Herein, we propose how homocysteinylation of the folate receptor may contribute to generation of these autoantibodies against the folate receptor.

Original languageEnglish (US)
Pages (from-to)1717-1727
Number of pages11
JournalClinical Chemistry and Laboratory Medicine
Issue number12
StatePublished - Dec 1 2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Clinical Biochemistry
  • Biochemistry, medical


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