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Mol Hum Reprod ; 18(5): 253-64, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22180326

RESUMEN

Maternal diabetes increases the risk of embryo malformations. Folic acid and safflower oil supplementations have been shown to reduce embryo malformations in experimental models of diabetes. In this study we here tested whether folic acid and safflower oil supplementations interact to prevent embryo malformations in diabetic rats, and analyzed whether they act through the regulation of matrix metalloproteinases (MMPs), their endogenous inhibitors (TIMPs), and nitric oxide (NO) and reactive oxygen species production. Diabetes was induced by streptozotocin administration prior to mating. From Day 0.5 of pregnancy, rats did or did not receive folic acid (15 mg/kg) and/or a 6% safflower oil-supplemented diet. Embryos and decidua were explanted on Day 10.5 of gestation for further analysis of embryo resorptions and malformations, MMP-2 and MMP-9 activities, TIMP-1 and TIMP-2 levels, NO production and lipid peroxidation. Maternal diabetes induced resorptions and malformations that were prevented by folic acid and safflower oil supplementation. MMP-2 and MMP-9 activities were increased in embryos and decidua from diabetic rats and decreased with safflower oil and folic acid supplementations. In diabetic animals, the embryonic and decidual TIMPs were increased mainly with safflower oil supplementation in decidua and with folic acid in embryos. NO overproduction was decreased in decidua from diabetic rats treated with folic acid alone and in combination with safflower oil. These treatments also prevented increases in embryonic and decidual lipid peroxidation. In conclusion, folic acid and safflower oil supplementations interact and protect the embryos from diabetes-induced damage through several pathways related to a decrease in pro-inflammatory mediators.


Asunto(s)
Diabetes Mellitus Experimental/complicaciones , Suplementos Dietéticos , Ácido Fólico/uso terapéutico , Embarazo en Diabéticas , Efectos Tardíos de la Exposición Prenatal/tratamiento farmacológico , Sustancias Protectoras/uso terapéutico , Aceite de Cártamo/uso terapéutico , Animales , Anomalías Congénitas/etiología , Anomalías Congénitas/prevención & control , Embrión de Mamíferos/efectos de los fármacos , Embrión de Mamíferos/metabolismo , Desarrollo Embrionario/efectos de los fármacos , Femenino , Reabsorción del Feto/prevención & control , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Óxido Nítrico/metabolismo , Embarazo , Resultado del Embarazo , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo
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