Increased sphingoid base‐1‐phosphates and failure of neural tube closure after exposure to fumonisin or FTY720

Waes, Janée Gelineau-van; Rainey, Mark A.; Maddox, Joyce R.; Voss, Kenneth A.; Sachs, Andrew J.; Gardner, Nicole M.; Wilberding, Justin; Riley, Ronald T.

doi:10.1002/bdra.23074

Cited by 47 publications

(41 citation statements)

References 84 publications

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“…Ceramides have never been explored as being causative for NTDs, with only a few reports implicating components of the sphingolipid metabolism pathway. 49,50 Environmental influences such as oxidative stress, have been welldocumented in cases of NTDs, such as those associated with exposure with valproic acid, 51 benzo-pyrenes, 52 arsenic, 53 and in cases of folate deficiency. 54 Interestingly, ceramides have been associated with oxidative stress.…”

Section: Ceramidesmentioning

confidence: 99%

Ceramide: a novel inducer for neural tube defects

Ross

Piorczynski

Harvey

et al. 2019

Developmental Dynamics

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Background Circulating plasma ceramides, a class of bioactive sphingolipids, are elevated in metabolic disorders, including obesity. Infants of women with these disorders are at 2‐ to 3‐fold greater risk for developing a neural tube defect (NTD). This study aimed to test the effects of embryonic exposure to C2‐ceramides (C2) during neural tube closure. Preliminary data shows an increase in NTDs in chick embryos after C2 exposure, and addresses potential mechanisms. Results Cell and embryo models were used to examine redox shifts after ceramide exposure. While undifferentiated P19 cells were resistant to ceramide exposure, neuronally differentiated P19 cells exhibited an oxidizing shift. Consistent with these observations, GSH E h curves revealed a shift to a more oxidized state in C2 treated embryos without increasing apoptosis or changing Pax3 expression, however cell proliferation was lower. Neural tube defects were observed in 45% of chick embryos exposed to C2, compared to 12% in control embryos. Conclusions C2 exposure during critical developmental stages increased the frequency of NTDs in the avian model. Increased ROS generation in cell culture, along with the more oxidative GSH E h profiles of C2 exposed cells and embryos, support a model wherein ceramide affects neural tube closure via altered tissue redox environments.

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Section: Ceramidesmentioning

confidence: 99%

Ceramide: a novel inducer for neural tube defects

Ross

Piorczynski

Harvey

et al. 2019

Developmental Dynamics

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“…Studies in mice have shown that FB 1 can induce NTD via disruption of sphingolipid metabolism (reviewed in ). Treatment with FB 1 results in depletion of complex sphingolipids and elevation in sphingoid bases and sphingoid base 1‐phosphates in maternal and fetal tissues .…”

Section: Introductionmentioning

confidence: 99%

Urinary fumonisin B₁ and estimated fumonisin intake in women from high‐ and low‐exposure communities in Guatemala

Torres

Matute

Waes

et al. 2013

Molecular Nutrition Food Res

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In Jutiapa, agroecological conditions favored FB production. UFB1 mirrored the estimated FB intake. UFB1 > 0.1 ng/mL resulted in a dose-dependent increase in the risk of exceeding FB intake of 2 μg/kg b.w./day compared to women with no detectable UFB1 . More than 50% exceeded 2 μg/kg b.w./day when UFB1 was >0.5 ng/mL. UFB2 and UFB3 were rarely detected confirming that FB1 is either absorbed better or preferentially excreted in urine.

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“…NTDs are generally recognized to result from complex gene–nutrient–environment interactions . Environmental toxins also contribute to risk in limited and specific contexts, such as the contamination of corn‐based products with the mycotoxin fumonisin or arsenic exposure . Current knowledge does not allow a priori identification of women who are at risk of folic acid–responsive NTDs.…”

Section: Unique Aspects Of Folic Acid Fortificationmentioning

confidence: 99%

Safety of folic acid

Field

Stover

2017

Annals of the New York Academy of Sciences

129

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There is a large body of literature demonstrating the efficacy of maternal folic acid intake in preventing birth defects, as well as investigations into potential adverse consequences of consuming folic acid above the upper level of intake (UL). Recently, two authoritative bodies convened expert panels to assess risks from high intakes of folic acid: the United States’ National Toxicology Program (NTP) and the United Kingdom’s Scientific Advisory Committee on Nutrition (SACN). Overall, the totality of the evidence examined by these panels, as well as studies published since the release of their reports, have not established risks for adverse consequences resulting from existing mandatory folic acid fortification programs that have been implemented in many countries. Current folic acid fortification programs have been shown to support public health in populations, and the exposure levels are informed by and adherent to the precautionary principle. Additional research is needed to assess the health effects of folic acid supplement use when the current upper limit for folic acid is exceeded.

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Increased sphingoid base‐1‐phosphates and failure of neural tube closure after exposure to fumonisin or FTY720

Abstract: Elevated sphingoid base-1-P after FB(1) or FTY720 suggest a potential role for these bioactive lipid ligands and activation of S1P receptor signaling pathways in the failure of neural tube closure after FB(1) or FTY720. Sa1P may represent a biomarker for FB(1)-NTD risk assessment.

Cited by 47 publications

References 84 publications

Ceramide: a novel inducer for neural tube defects

Ceramide: a novel inducer for neural tube defects

Urinary fumonisin B₁ and estimated fumonisin intake in women from high‐ and low‐exposure communities in Guatemala

Safety of folic acid

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Increased sphingoid base‐1‐phosphates and failure of neural tube closure after exposure to fumonisin or FTY720

Abstract: Elevated sphingoid base-1-P after FB(1) or FTY720 suggest a potential role for these bioactive lipid ligands and activation of S1P receptor signaling pathways in the failure of neural tube closure after FB(1) or FTY720. Sa1P may represent a biomarker for FB(1)-NTD risk assessment.

Cited by 47 publications

References 84 publications

Ceramide: a novel inducer for neural tube defects

Ceramide: a novel inducer for neural tube defects

Urinary fumonisin B1 and estimated fumonisin intake in women from high‐ and low‐exposure communities in Guatemala

Safety of folic acid

Contact Info

Product

Resources

About

Urinary fumonisin B₁ and estimated fumonisin intake in women from high‐ and low‐exposure communities in Guatemala