Maternal diet alters exencephaly frequency in SELH/Bc strain mouse embryos.
BACKGROUND
The SELH/Bc mouse inbred strain, with a high frequency of nonsyndromic, genetically-multifactorial exencephaly, is a model for human cranial neural tube defects (NTDs). Maternal diet affects risk of human NTDs.


METHODS
Exencephaly frequencies in SELH/Bc embryos were compared in 8 studies in which dams were fed alternative commercial Purina diets (5015 and 5001) or semisynthetic diets, and in several studies in which maternal diet was supplemented with a specific nutrient, either in drinking water or food before and during pregnancy, or by intraperitoneal injection on E7 and/or E8.


RESULTS
The exencephaly frequency in SELH/Bc embryos was 2- to 8-fold higher when the dams were fed Purina 5015 (averaging 23% exencephaly) or a semisynthetic diet modeled on Purina 5015 (averaging 28%) or NIH-31 standard diet (23%), compared with Purina 5001 (averaging 7%). The exencephaly frequency remained high (41%) on a semisynthetic diet modeled on Purina 5001. The exencephaly frequency was not reduced significantly by maternal supplementation with folic acid, nor with each of zinc, methionine, niacin, brewers' yeast, riboflavin, vitamin B12, or inositol. Nor was it reduced by maternal diets with supplemental methyl donors and cofactors or with reduced fat.


CONCLUSIONS
The frequency of exencephaly in SELH/Bc embryos is strongly influenced by a specific unidentified aspect of the commercial ration Purina 5001 that prevents 55-85% of exencephaly in SELH/Bc embryos, when directly compared with an alternative commercial ration Purina 5015 or its semisynthetic mimic. This strong maternal diet effect on NTD frequency may point to novel nutritional approaches to prevention of human NTDs.
Harris
Muriel J
MJ
Department of Medical Genetics, University of British Columbia, Vancouver, Canada. mjharris@interchange.ubc.ca
Juriloff
Diana M
DM
D000818:Animals; D003389:Cranial Nerve Diseases / Q000209:etiology / Q000517:prevention & control; D004032:Diet; D004035:Diet Therapy / Q000379:methods; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004622:Embryo, Mammalian / Q000473:pathology; D005260:Female; D005315:Fetal Diseases / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D039382:Maternal Nutritional Physiological Phenomena; D051379:Mice; D008815:Mice, Inbred Strains; D009436:Neural Tube Defects / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D011247:Pregnancy; D012307:Risk Factors