Your browser doesn't support javascript.
loading
Metabolite profiling of whole murine embryos reveals metabolic perturbations associated with maternal valproate-induced neural tube closure defects.
Akimova, Darya; Wlodarczyk, Bogdan J; Lin, Ying; Ross, M Elizabeth; Finnell, Richard H; Chen, Qiuying; Gross, Steven S.
Afiliación
  • Akimova D; Department of Pharmacology, Weill Cornell Medical College, New York, New York.
  • Wlodarczyk BJ; Program in Pharmacology, Weill Cornell Medical College, New York, New York.
  • Lin Y; Department of Nutritional Sciences, Dell Pediatric Research Institute, The University of Texas at Austin, Austin, Texas.
  • Ross ME; Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, New York.
  • Finnell RH; Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, New York.
  • Chen Q; Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, New York.
  • Gross SS; Department of Pharmacology, Weill Cornell Medical College, New York, New York.
Birth Defects Res ; 109(2): 106-119, 2017 01 30.
Article en En | MEDLINE | ID: mdl-27860192
BACKGROUND: Valproic acid (VPA) is prescribed therapeutically for multiple conditions, including epilepsy. When taken during pregnancy, VPA is teratogenic, increasing the risk of several birth and developmental defects including neural tube defects (NTDs). The mechanism by which VPA causes NTDs remains controversial and how VPA interacts with folic acid (FA), a vitamin commonly recommended for the prevention of NTDs, remains uncertain. We sought to address both questions by applying untargeted metabolite profiling analysis to neural tube closure (NTC) stage mouse embryos. METHODS: Pregnant SWV dams on either a 2 ppm or 10 ppm FA supplemented diet were injected with a single dose of VPA on gestational day E8.5. On day E9.5, the mouse embryos were collected and evaluated for NTC status. Liquid chromatography coupled to mass spectrometry metabolomics analysis was performed to compare metabolite profiles of NTD-affected VPA-exposed whole mouse embryos with profiles from embryos that underwent normal NTC from control dams. RESULTS: NTDs were observed in all embryos from VPA-treated dams and penetrance was not diminished by dietary FA supplementation. The most profound metabolic perturbations were found in the 10ppm FA VPA-exposed mouse embryos, compared with the other three treatment groups. Affected metabolites included amino acids, nucleobases and related phosphorylated nucleotides, lipids, and carnitines. CONCLUSION: Maternal VPA treatment markedly perturbed purine and pyrimidine metabolism in E9.5 embryos. In combination with a high FA diet, VPA treatment resulted in gross metabolic changes, likely caused by a multiplicity of mechanisms, including an apparent disruption of mitochondrial beta-oxidation. Birth Defects Research 109:106-119, 2017. © 2016 Wiley Periodicals, Inc.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Teratógenos / Ácido Valproico / Suplementos Dietéticos / Neurulación / Ácido Fólico / Defectos del Tubo Neural Tipo de estudio: Risk_factors_studies Límite: Animals / Pregnancy Idioma: En Revista: Birth Defects Res Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Teratógenos / Ácido Valproico / Suplementos Dietéticos / Neurulación / Ácido Fólico / Defectos del Tubo Neural Tipo de estudio: Risk_factors_studies Límite: Animals / Pregnancy Idioma: En Revista: Birth Defects Res Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos