TY - CHAP
T1 - Chapter 5 Maternal Fumonisin Exposure as a Risk Factor for Neural Tube Defects
AU - Gelineau-van Waes, J.
AU - Voss, K. A.
AU - Stevens, V. L.
AU - Speer, M. C.
AU - Riley, R. T.
PY - 2009
Y1 - 2009
N2 - 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 metabolites (i.e., sphinganine-1-phosphate) 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 exposures 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.
AB - 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 metabolites (i.e., sphinganine-1-phosphate) 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 exposures 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.
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U2 - 10.1016/S1043-4526(08)00605-0
DO - 10.1016/S1043-4526(08)00605-0
M3 - Chapter
C2 - 19389609
AN - SCOPUS:64749088908
SN - 9780123744395
T3 - Advances in Food and Nutrition Research
SP - 145
EP - 181
BT - Advances in Food and Nutrition Research
A2 - Taylor, Steve
ER -