Hypothesis: Folate-responsive neural tube defects and neurocristopathies

Aśok C. Antony, Deborah K. Hansen

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

Background: What accounts for the wide spectrum of folate-responsive dysmorphogeneses? Both embryonic and fetal cells are entirely dependent on maternal folate to support their requirement for precisely timed proliferative bursts during gestation. Folate receptors (FRs) mediate transport into cells and are central to transplacental maternal-to-fetal folate transport. FRs are also critical for neural tube and neural crest development because recent murine 'knock-out' and 'knock-down' of FRs results in a high percentage of folate-responsive neural tube defects (NTDs) and neurocristopathies. Hypothesis: Central to our hypothesis is the fact that folate deficiency is accompanied by a reduction in the proliferative capacity of highly mitotic neural tube or neural crest cells. Therefore, depending on when in pregnancy various cohorts of highly proliferative cells are deprived of folate, and the origin of the affected cells will determine the type of developmental dysmorphogenesis. Thus, selective folate deficiency in early pregnancy of only highly proliferative neural tube or neural crest cells predisposes to NTDs or gross dysmorphogenesis, respectively. Folate deficiency that compromises placental development will predispose to small-for-date babies due to an overall nutrient deficiency, and the development of folate insufficiency later in pregnancy could predispose to more subtle midline birth defects involving atresia of neural crest cell-derived structures. Finally, a congenital folate transport defect would only be corrected by supra-pharmacological doses of folate, which ensures passive diffusion. Conclusion: This hypothesis can explain the results of several earlier and more recent clinical trials on folate supplementation in pregnancy, but it also raises the possibility that there may be several as yet undiscovered neurocristopathies that are folate responsive.

Original languageEnglish (US)
Pages (from-to)42-50
Number of pages9
JournalTeratology
Volume62
Issue number1
DOIs
StatePublished - Jul 19 2000

ASJC Scopus subject areas

  • Embryology
  • Toxicology
  • Developmental Biology
  • Health, Toxicology and Mutagenesis

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