Submitted to: Molecular Nutrition and Food Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: January 13, 2014
Publication Date: June 1, 2014
Citation: Voss, K.A., Riley, R.T., Gelineau-Van Waes, J. 2014. Fumonisin B1 induced neural tube defects were not increased in LM/Bc mice fed folate-deficient diet. Molecular Nutrition and Food Research. 58:1190-1198. Interpretive Summary: Fumonisin B1 (FB1) is a mycotoxin found in corn and foods. There is evidence that FB1 increases the risk of birth defects known as neural tube defects, including within populations that consume large amounts of alkaline cooked corn as a diet staple. Dietary folate protects against neural tube defects but its amounts are reduced in alkaline cooked corn. It is not known how folate deficiency influences the induction of neural tube defects by FB1 in the LM/Bc mouse, a strain that is sensitive to the effects of FB1. Female LM/Bc mice were fed control or folate deficient diets beginning five weeks before they were paired with males. Groups of pregnant mice were then given graded doses (0, 2.5 or 10 mg/kg body weight) of FB1 at the critical time during gestation for correct neural tube development. The folate deficient diet reduced blood folate levels in the pregnant mice by 80 percent whereas FB1 had no effect on blood folate. At the same time, decreased numbers of litters having one or more neural tube defect-affected fetuses and decreased numbers of affected fetuses per litter were found in groups fed the deficient diet. Fetal death rates, while slightly higher in the litters of females fed deficient diet, did not account entirely for the reduced rates of neural tube defects, indicating that other mechanisms are likely involved. Genetic, environmental and nutritional factors contributing to neural tube defects are complex and further studies are needed to determine how FB1 and folate interact to affect fetal development in this mouse model and the suitability of this model for human risk assessment of FB1.
Technical Abstract: Fumonisin B1 (FB1) is a mycotoxin produced by Fusarium verticillioides that is found in corn-based foods and is possibly a risk factor for neural tube defects (NTD). The mechanism(s) underlying NTD induction by FB1 in the sensitive LM/Bc mouse model is not well understood, however, there is evidence suggesting that disrupted folate transport is involved. To further explore the role of folate, female LM/Bc mice were fed control or folate deficient diets. After five weeks, they were mated, assigned to groups (3 groups/diet; n=9-13 dams/group) and treated with 0 (vehicle), 2.5 or 10 mg/kg FB1 by intraperitoneal injection on embryonic days 7 (E7) and E8. The folate deficient diet had no adverse effect before or during gestation. Fetuses were examined on E16 and a dose dependent increase in NTD induction was found in groups fed the control diets: 3 of 13 (23%) low dose and 10 of 11 (91%) high dose litters were affected. Among the groups fed folate deficient diet, NTD were found only in 4 of 11 (36%) high-dose litters. In a second trial, consumption of the folate deficient diet also protected against NTD induction by 10 mg/kg FB1 while reducing maternal red blood cell folate levels by 80%. In utero death rates, although modestly increased, did not account for the difference in NTD rates in the first trial. Folate deficiency does not exacerbate NTD induction by FB1 in the sensitive LM/Bc mouse model. Interactions between folate, other nutritional factors, and FB1 in the LM/Bc mouse model for NTD are complex and require further investigation.