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Title: Maternal fumonisin exposure as a risk factor for neural tube defects

Author
item GELINEAU-VAN WAES, J - Nebraska Medical Center
item Voss, Kenneth
item STEVENS, V - Nebraska Medical Center
item SPEER, M - Nebraska Medical Center
item Riley, Ronald

Submitted to: Book Chapter
Publication Type: Book / Chapter
Publication Acceptance Date: 8/27/2008
Publication Date: 7/15/2009
Citation: Gelineau-Van Waes, J., Voss, K.A., Stevens, V.L., Speer, M.C., Riley, R.T. 2009. Maternal fumonisin exposure as a risk factor for neural tube defects. In: Taylor, S., editor. Advances in Food and Nutrition Research. Volume 56. Amsterdam, The Netherlands:Elsevier/Academic Press. p.145-181.

Interpretive Summary: Fumonisins are toxic chemicals produced by the fungus Fusarium verticillioides, a common contaminant of maize (corn) worldwide. Maternal consumption of fumonisin B1-contaminated maize during early pregnancy has recently been suggested to be a possible risk factor for birth defects known as neural tube defects (NTDs) in human populations that rely heavily on maize as a dietary staple and where diets are likely to be deficient in vitamins known to protect against NTD. One vitamin that is critical for reducing NTD risk is folic acid. Administration of purified fumonisin to certain strains of mice early in gestation results in an increased incidence of NTDs in exposed offspring. Fumonisin blocks the formation of an important group of fats known as sphingolipids. When fumonisin blocks the formation of sphingolipids there is also an increase in certain sphingolipid metabolites that can cause changes in cell survival. Increased sphingolipid metabolites may alter the signaling processes involved in embryonic development. There is also a decrease in sphingolipids that are known to be necessary for the transport of folate. NTDs appear to be multifactorial in origin, involving complex gene-nutrient-environment interactions. Vitamin supplements containing folic acid have been shown to reduce the occurrence of NTDs and may help protect the developing fetus from environmental teratogens. Fumonisins may be an environmental risk factor for birth defects, although other aspects of maternal nutrition and genetics play interactive roles in determining pregnancy outcome. Minimizing exposure to mycotoxins through enhanced agricultural practices, identifying biomarkers of exposure, characterizing mechanisms of toxicity, and improving maternal nutrition are all important strategies for reducing the NTD burden in susceptible human populations.

Technical Abstract: Fumonisins are mycotoxins produced by the fungus F. verticillioides, a common contaminant of maize (corn) worldwide. Maternal consumption of fumonisin B1-contaminated maize during early pregnancy has recently been associated with increased risk for neural tube defects (NTDs) in human populations that rely heavily on maize as a dietary staple. Experimental administration of purified fumonisin to mice early in gestation also results in an increased incidence of NTDs in exposed offspring. Fumonisin inhibits the enzyme ceramide synthase in de novo sphingolipid biosynthesis, resulting in an elevation of free sphingoid bases and depletion of downstream glycosphingolipids. Increased sphingoid base metabolies (ie.sphinganine-1-phosphte) may perturb signaling cascades involved in embryonic morphogenesis by functioning as ligands for sphingosine-1-P (S1P) receptors, a family of G-protein-coupled receptors that regulate key biological processes such as cell survival/proliferation, differentiation and migration. Fumonisin-induced depletion of glycosphingolipids impairs expression and function of the GPI-anchored folate receptor (Folr1), which may also contribute to adverse pregnancy outcomes. NTDs appear to be multifactorial in origin, involving complex gene-nutrient-environment interactions. Vitamin supplements containing folic acid have been shown to reduce the occurrence of NTDs, and may help protect the developing fetus from environmental teratogens. Fumonisins appear to be an environmental risk factor for birth defects, although other aspects of maternal nutrition and genetics play interactive roles in determining pregnancy outcome. Minimizing exposure to mycotoxins through enhanced agricultural practices, identifying biomarkers of exposure, characterizing mechanisms of toxicity, and improving maternal nutrition are all important strategies for reducting the NTD burden in susceptible human populations.