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ARS Home » Southeast Area » Athens, Georgia » U.S. National Poultry Research Center » Toxicology & Mycotoxin Research » Research » Publications at this Location » Publication #301503
Title: Fumonisins as a potential risk factor for neural tube defects: a review

Author
item Voss, Kenneth
item Riley, Ronald
item GELINEAU-VAN WAES, JANEE - Creighton University
item TORRES, OLGA - National Institute Of Public Health (INSP)

Submitted to: United States-Japan Cooperative Program in Natural Resources (UJNR)
Publication Type: Abstract Only
Publication Acceptance Date: 1/26/2014
Publication Date: 1/26/2014
Citation: Voss, K.A., Riley, R.T., Gelineau-Van Waes, J., Torres, O. 2014. Fumonisins as a potential risk factor for neural tube defects: a review. United States-Japan Cooperative Program in Natural Resources (UJNR). January 26-31,2014. Tokyo/Shizuoka, Japan.

Interpretive Summary: Abstract - no summary required.

Technical Abstract: Fumonisins are produced by Fusarium verticillioides and F. proliferatum, fungi that commonly contaminate maize and maize-based foods. Fumonisin B1 (FB1), the most common congener, causes species-specific diseases in farm and laboratory animals. Its health effects in humans remain unknown; however, experimental and epidemiological evidence suggest that FB1 is a potential risk factor for neural tube defects (NTD; birth defects from the failure of neural tube closure), particularly in populations whose diet depends on staple foods made from fumonisin-contaminated maize. Therefore, studies have been done using the LM/Bc mouse strain to explore mechanisms of FB1-dependent NTD induction; to study interactions between FB1 and folic acid (a vitamin that reduces NTD risk) during NTD induction; to determine if hydrolyzed FB1 (HFB1; formed from FB1 during alkaline cooking) also causes NTD; and to develop urinary FB1 as a biomarker of exposure and sphingoid base 1-phosphates as biomarkers for ceramide synthase inhibition. Results have shown that: (a) FB1 inhibits ceramide synthase thereby reversibly increasing sphinganine (Sa), sphinganine-1-phosphate (Sa-1-P) and sphingosine-1-phosphate (So-1-P) as well as decreasing complex sphingolipids; (b) the So-1-P analog FTY720, like FB1, causes NTD, therefore suggesting a mechanistic role for perturbed So(Sa)-1-P signaling in failed neural tube closure; (c) co-exposure to FB1 and folic acid (maternal folic acid supplementation reduces the risk of NTD pregnancy outcomes) or the complex lipid GM1 protects against NTD induction by the mycotoxin; however, depletion of maternal blood folate (ca. 80 percent reduction) by consumption of folic acid-deficient diet (alkaline cooking destroys folic acid) did not increase NTD induction by FB1; and (d) HFB1 did not induce NTD, thus indicating that alkaline cooking reduces NTD risk. An LC-MS method for quantifying fumonisins in urine has been developed and utilized in a study of urinary fumonisins in volunteers from six departments of Guatemala, a country in which NTD are relatively common. Key findings were that: (a) urinary FB1 concentrations were relatively high in the three departments where FB1 levels in maize were highest; (b) total urinary fumonisins (FB1 + fumonisin B2 + fumonisin B3) and total fumonisin intake of volunteers (calculated from fumonisin concentrations in maize, estimated maize consumption of the volunteers, and the volunteers' body weights) rose together in a dose-dependent manner; and (c) the contribution of FB1 to total fumonisins in urine was disproportionately high compared to its contribution to total fumonisins in maize. Preliminary analysis indicates that urinary FB1 levels and levels of sphingoid base 1-phosphates in blood spots are significantly correlated. These findings contribute to an integrated approach aimed at understanding nutritional and mechanistic factors influencing FB1-dependent NTD induction in mice and ultimately to determine those that are relevant to humans.