Effects of folate supplementation on the risk of spontaneous and induced neural tube defects in Splotch mice.
BACKGROUND
Neural tube defects (NTDs) are among the most common human congenital malformations. Although clinical investigations have reported that periconceptional folic acid supplementation can reduce the occurrence of these defects, its mechanism remains unknown. Therefore, the murine mutant Splotch, which has a high incidence of spontaneous NTDs, along with the inbred strains SWV and LM/Bc, were used to investigate the relationship between folate and NTDs.


METHODS
To investigate whether folates could reduce spontaneous NTDs, heterozygous Splotch dams (+/Sp) were treated with either folate or folinic acid throughout neurulation, gestational day (GD) 6.5 to 10.5. On GD 18.5 the dams were sacrificed and the fetuses examined for any neural tube defects. Subsequently, Sp/+ dams were treated with arsenic while receiving either a folate or folinic acid supplementation. Similar experiments were performed in the LM/Bc and SWV strains.


RESULTS
Neither folate nor folinic acid supplements reduced the frequency of spontaneous NTDs in the embryos from Splotch heterozygote crosses. Arsenic increased the frequency of NTDs and embryonic death in the Splotch, LM/Bc and SWV litters and folinic acid failed to ameliorate the teratogenic effect of this metal. A folate supplement given to arsenic-treated dams proved to be maternally lethal in all three strains.


CONCLUSIONS
Splotch embryos were not protected from either spontaneous or arsenic-induced NTDs by folinic or folic acid supplementation. Furthermore, folinic acid supplements did not reduce the incidence of arsenic-induced NTDs in either the LM/Bc or SWV litters.
Gefrides
Lisa A
LA
Department of Veterinary Anatomy and Public Heath, Texas A&M University, College Station, Texas 77843-4458, USA.
Bennett
Gregory D
GD
Finnell
Richard H
RH
D000818:Animals; D001149:Arsenates; D004268:DNA-Binding Proteins / Q000502:physiology; D020964:Embryo Loss; D005260:Female; D005327:Fetal Resorption; D005492:Folic Acid / Q000502:physiology / Q000627:therapeutic use*; D005838:Genotype; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009436:Neural Tube Defects / Q000235:genetics / Q000517:prevention & control*; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D013723:Teratogens; D014157:Transcription Factors
D001149:Arsenates; D004268:DNA-Binding Proteins; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051761:Paired Box Transcription Factors; D013723:Teratogens; D014157:Transcription Factors; C068686:Pax3 protein, mouse; D005492:Folic Acid; C025657:arsenic acid; D002955:Leucovorin