Location: Toxicology and Mycotoxin Research
Title: Neural Tube Defect Induction by Fumonisin B1 in LM/Bc Mice Fed Folate Deficient or Folate Replete Diets Authors
Submitted to: United States-Japan Cooperative Program in Natural Resources (UJNR)
Publication Type: Abstract Only
Publication Acceptance Date: December 15, 2012
Publication Date: January 27, 2013
Citation: Voss, K.A., Riley, R.T., Gelineau-Van, W.J. 2013. Neural Tube Defect Induction by Fumonisin B1 in LM/Bc Mice Fed Folate Deficient or Folate Replete Diets [abstract]. United States-Japan Cooperative Program in Natural Resources (UJNR). p. 34. Interpretive Summary: Abstract - no summary required.
Technical Abstract: Fumonisin B1 (FB1) is a mycotoxin produced by Fusarium verticillioides and F. proliferatum. FB1 is found in corn-based foods and evidence suggests that it is 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, partial reversal of NTD by the co-administration of folic acid and almost complete reversal by co-administration of the complex sphingolipid GM1 suggests disrupted folate uptake and utilization and depletion of complex sphingolipids associated with the GPI-anchored folate receptor are involved. To further explore the role of folate in NTD induction by FB1, female LM/Bc mice were fed control (folate sufficient) or folate deficient diets beginning five weeks before mating (to untreated males) and continuing until the end of the study. The females were assigned to groups (3 groups/diet; n=9-13 dams/group) on the day of mating (embryonic day 0 = E0), and given 0 (vehicle), 2.5 or 10 mg/kg FB1 by intraperitoneal injection on E7 and E8. Dams and litters were examined at necropsy on E16. The folate deficient diet had no adverse effect on the dams before or during gestation. NTD, which exhibited as exencephaly, were found in litters of control diet-fed dams given greater than or equal to 2.5 mg/kg FB1. The effect was dose-dependent: at least one NTD-affected fetus was found in 3 of 13 (23% incidence) litters at the low dose and 10 of 11 (91% incidence) litters at the high dose. Among the groups fed folate deficient diet, NTD were found in 4 of 11 (36% incidence) litters at the high dose of 10 mg/kg FB1 but were not found at doses of less than or equal to 2.5 mg/kg FB1. Mean in utero death rates (resorptions plus late deaths) were numerically higher in the litters of dams fed folate deficient diet than in their corresponding control diet groups; however the difference was not statistically significant. In summary, long-term consumption of folate deficient diet did not increase the likelihood of NTD following FB1 exposure. Mechanistic interactions between folate, other metabolic factors, and FB1 during NTD induction in the LM/Bc mouse model are complex, remain poorly understood, and require further investigation.