title: Fumonisins disrupt sphingolipid metabolism, folate transport, and neural tube development in embryo culture and in vivo: a potential risk factor for human neural tube defects among populations consuming fumonisin-contaminated maize.
abstract: Fumonisins are a family of toxic and carcinogenic mycotoxins produced by Fusarium verticillioides (formerly Fusarium moniliforme), a common fungal contaminant of maize. Fumonisins inhibit ceramide synthase, causing accumulation of bioactive intermediates of sphingolipid metabolism (sphinganine and other sphingoid bases and derivatives) as well as depletion of complex sphingolipids, which interferes with the function of some membrane proteins, including the folate-binding protein (human folate receptor alpha). Fumonisin causes neural tube and craniofacial defects in mouse embryos in culture. Many of these effects are prevented by supplemental folic acid. Recent studies in LMBc mice found that fumonisin exposure in utero increases the frequency of developmental defects and administration of folate or a complex sphingolipid is preventive. High incidences of neural tube defects (NTD) occur in some regions of the world where substantial consumption of fumonisins has been documented or plausibly suggested (Guatemala, South Africa, and China); furthermore, a recent study of NTD in border counties of Texas found a significant association between NTD and consumption of tortillas during the first trimester. Hence, we propose that fumonisins are potential risk factors for NTD, craniofacial anomalies, and other birth defects arising from neural crest cells because of their apparent interference with folate utilization.
authors.affiliation: Medical Research Council, PROMEC Unit, Tygerberg 7505, South Africa. wally.marasas@mrc.ac.za
authors.forename: Walter F O
authors.initials: WF
authors.lastname: Marasas
authors.forename: Ronald T
authors.initials: RT
authors.lastname: Riley
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Hendricks
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Stevens
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Sadler
authors.forename: Janee
authors.initials: J
authors.lastname: Gelineau-van Waes
authors.forename: Stacey A
authors.initials: SA
authors.lastname: Missmer
authors.forename: Julio
authors.initials: J
authors.lastname: Cabrera
authors.forename: Olga
authors.initials: O
authors.lastname: Torres
authors.forename: Wentzel C A
authors.initials: WC
authors.lastname: Gelderblom
authors.forename: Jeremy
authors.initials: J
authors.lastname: Allegood
authors.forename: Carolina
authors.initials: C
authors.lastname: Martínez
authors.forename: Joyce
authors.initials: J
authors.lastname: Maddox
authors.forename: J David
authors.initials: JD
authors.lastname: Miller
authors.forename: Lois
authors.initials: L
authors.lastname: Starr
authors.forename: M Cameron
authors.initials: MC
authors.lastname: Sullards
authors.forename: Ana Victoria
authors.initials: AV
authors.lastname: Roman
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Voss
authors.forename: Elaine
authors.initials: E
authors.lastname: Wang
authors.forename: Alfred H
authors.initials: AH
authors.lastname: Merrill
mesh_terms: D000818:Animals; D001692:Biological Transport; D019465:Craniofacial Abnormalities / Q000139:chemically induced; D046508:Culture Techniques; D004195:Disease Models, Animal; D005492:Folic Acid / Q000378:metabolism*; D005506:Food Contamination; D037341:Fumonisins / Q000494:pharmacology*; D006801:Humans; D008800:Mexico; D051379:Mice; D009436:Neural Tube Defects / Q000139:chemically induced*; D012307:Risk Factors; D013107:Sphingolipids / Q000378:metabolism*; D013781:Texas; D003313:Zea mays
chemical_list: D037341:Fumonisins; D013107:Sphingolipids; D005492:Folic Acid