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Prevention of Teratogenesis in Pregnancies of Obese Rats by Vitamin E Supplementation.
Alcala, Martin; Bolado, Victoria E; Sánchez-Vera, Isabel; Clapés, Sonia; Dasí, Francisco; Sáez, Guillermo; Carrera, Esther; Alvarez-Gallego, Fabiola; Loeken, Mary R; Viana, Marta.
Afiliação
  • Alcala M; Departamento de Química y Bioquímica, Facultad de Farmacia, Universidad CEU-San Pablo, CEU Universities, 28668 Madrid, Spain.
  • Bolado VE; Laboratorio de Investigación Genómica y Fisiológica, Facultad de Nutrición, Universidad Veracruzana, Xalapa 91090, Mexico.
  • Sánchez-Vera I; Departamento de Ciencias Médicas Básicas, Facultad de Medicina, Universidad CEU-San Pablo, CEU Universities, 28668 Madrid, Spain.
  • Clapés S; Departamento de Bioquímica del Instituto de Ciencias Básica y Preclínica "Victoria de Girón", Universidad de Ciencias Médicas de la Habana, La Habana 10699, Cuba.
  • Dasí F; Department of Physiology, Instituto de Investigación Sanitaria INCLIVA, University of Valencia, 46010 Valencia, Spain.
  • Sáez G; Departamento de Bioquímica y Biología Molecular, Facultad de Medicina y Odontología-INCLIVA, Servicio de Análisis Clínicos, Hospital Universitario Dr.Peset-FISABIO, Universitat de Valencia, 46017 Valencia, Spain.
  • Carrera E; Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad CEU-San Pablo, CEU Universities, 28668 Madrid, Spain.
  • Alvarez-Gallego F; Departamento de Química y Bioquímica, Facultad de Farmacia, Universidad CEU-San Pablo, CEU Universities, 28668 Madrid, Spain.
  • Loeken MR; Section on Islet Cell and Regenerative Biology, Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.
  • Viana M; Departamento de Química y Bioquímica, Facultad de Farmacia, Universidad CEU-San Pablo, CEU Universities, 28668 Madrid, Spain.
Antioxidants (Basel) ; 10(8)2021 Jul 23.
Article em En | MEDLINE | ID: mdl-34439421
ABSTRACT
Congenital malformations are a common adverse outcome in pregnancies complicated by pregestational obesity, although the underlying mechanisms are still unrevealed. Our aim was to study the effect of oxidative stress in obesity-induced teratogenesis. Wistar rats were fed a high-fat diet for 13 weeks, with (OE group) or without (O group) vitamin E supplementation. Then, rats were mated and sacrificed at day 11.5 of gestation. Embryos from O dams presented a 25.9 ± 3.5% rate of malformations (vs. 8.7 ± 3.4% in C rats), which was reduced in the OE group (11.5 ± 2.3%). Pregestational obesity induced hepatic protein and DNA oxidation and a decline in antioxidant enzymes. Importantly, glutathione content was also decreased, limiting the availability of this antioxidant in the embryos. Vitamin E supplementation efficiently maintained glutathione levels in the obese mothers, which could be used in their embryos to prevent oxidation-induced malformations. To test the effect of decreasing glutathione levels alone in a cell culture model of neuroepithelium, murine embryonic stem cells (ESC) were induced to form neuronal precursors and glutathione synthesis was inhibited with the gamma-glutamylcysteine synthesis inhibitor, buthionine sulfoximine (BSO). BSO inhibited the expression of Pax3, a gene required for neural tube closure that is also inhibited by oxidative stress. Taken together, our data indicate that obesity causes malformations through the depletion of maternal glutathione, thereby decreasing glutathione-dependent free radical scavenging in embryos, which can be prevented by vitamin E supplementation.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Revista: Antioxidants (Basel) Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Espanha

Texto completo: 1 Base de dados: MEDLINE Idioma: En Revista: Antioxidants (Basel) Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Espanha