This article is a US government work and, as such, is in the public domain in the United States of America.
Article first published online: 15 JUN 2005
Published 2005 Wiley-Liss, Inc.
Birth Defects Research Part A: Clinical and Molecular Teratology
Volume 73, Issue 7, pages 487–497, July 2005
How to Cite
Gelineau-van Waes, J., Starr, L., Maddox, J., Aleman, F., Voss, K. A., Wilberding, J. and Riley, R. T. (2005), Maternal fumonisin exposure and risk for neural tube defects: Mechanisms in an in vivo mouse model. Birth Defects Research Part A: Clinical and Molecular Teratology, 73: 487–497. doi: 10.1002/bdra.20148
Presented in part at the 2003 and 2004 Annual Meeting of the Teratology Society and the 2003 and 2004 Annual Meeting of the Society of Toxicology.
- Issue published online: 6 JUL 2005
- Article first published online: 15 JUN 2005
- Manuscript Accepted: 16 FEB 2005
- Manuscript Received: 24 SEP 2004
- Nebraska Research Initiative
- neural tube defects;
- lipid raft;
- ganglioside GM1
Fumonisin B1 (FB1) is a mycotoxin produced by the fungus Fusarium verticillioides, a common contaminant of corn worldwide. FB1 disrupts sphingolipid biosynthesis by inhibiting the enzyme ceramide synthase, resulting in an elevation of free sphingoid bases and depletion of downstream glycosphingolipids. A relationship between maternal ingestion of FB1-contaminated corn during early pregnancy and increased risk for neural tube defects (NTDs) has recently been proposed in human populations around the world where corn is a dietary staple. The current studies provide an in vivo mouse model of FB1 teratogenicity.
Pregnant LM/Bc mice were injected with increasing doses of FB1 on GD 7.5 and 8.5, and exposed fetuses were examined for malformations. Sphingolipid profiles and 3H-folate concentrations were measured in maternal and fetal tissues. Immunohistochemical expression of the GPI-anchored folate receptor (Folbp1) and its association with the lipid raft component, ganglioside GM1, were characterized. Rescue experiments were performed with maternal folate supplementation or administration of gangliosides.
Maternal FB1 administration (20 mg/kg of body weight) during early gestation resulted in 79% NTDs in exposed fetuses. Sphingolipid profiles were significantly altered in maternal and embryonic tissues following exposure, and 3H-folate levels and immunohistochemical expression of Folbp1 were reduced. Maternal folate supplementation partially rescued the NTD phenotype, whereas GM1 significantly restored folate concentrations and afforded almost complete protection against FB1-induced NTDs.
Maternal FB1 exposure altered sphingolipid metabolism and folate concentrations in LM/Bc mice, resulting in a dose-dependent increase in NTDs that could be prevented when adequate folate levels were maintained. Birth Defects Research (Part A), 2005. Published 2005 Wiley-Liss, Inc.