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.
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.
Marasas
Walter F O
WF
Medical Research Council, PROMEC Unit, Tygerberg 7505, South Africa. wally.marasas@mrc.ac.za
Riley
Ronald T
RT
Hendricks
Katherine A
KA
Stevens
Victoria L
VL
Sadler
Thomas W
TW
Gelineau-van Waes
Janee
J
Missmer
Stacey A
SA
Cabrera
Julio
J
Torres
Olga
O
Gelderblom
Wentzel C A
WC
Allegood
Jeremy
J
Martínez
Carolina
C
Maddox
Joyce
J
Miller
J David
JD
Starr
Lois
L
Sullards
M Cameron
MC
Roman
Ana Victoria
AV
Voss
Kenneth A
KA
Wang
Elaine
E
Merrill
Alfred H
AH
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
D037341:Fumonisins; D013107:Sphingolipids; D005492:Folic Acid