Maternal Treatments with Folic Acid and Safflower Oil Prevent Matrix Metalloproteinases Overactivity in the Embryo and Decidua from Diabetic Rats

HIGA,R; CAPOBIANCO E; KURTZ M; JAWERBAUM A

Santiago de Chile

Congreso; International Federation of Placental Associations IFPA Meeting 2010; 2010

IFPA

Introduction: Maternal diabetes induces embryo malformations, related to the intrauterine pro-inflammatory environment. Maternal treatments with folic acid and safflower oil (enriched in linoleic acid, an endogenous agonist of peroxisome proliferator activated receptors (PPARs)) can prevent congenital malformations, although the mechanisms involved are unclear. Matrix metalloproteinases (MMPs) are proteolytic enzymes involved in developmental processes that can be overactivated in a pro-inflammatory environment. Aim: To analyze the effects of maternal treatments with folic acid (FOL) and/or safflower oil (SAF) on oxidative stress and MMPs activities in the embryo and decidua from control and diabetic rats on day 10.5 of pregnancy. Methods: Diabetes was induced in rats by streptozotocin administration (50 mg/kg) prior to mating. Treatments with FOL (0.5% s.c.) and SAF (6%, dietary supplementantion) were given from days 0.5 to 10.5 of gestation. Isoprostanes and TBARs were measured as indexes of oxidative stress. MMP-2 and MMP-9 activities were measured by zymography. Results: Embryos from diabetic rats showed increased levels of isoprostanes (p<0.01) when compared to controls, whereas FOL and FOL+SAF treatments prevented these anomalies (p<0.001). TBARs were increased in decidua from diabetic rats (p<0.05) when compared to controls and were highly reduced by SAF, FOL and FOL+SAF (p<0.001). In embryos from diabetic rats MMP-2 and MMP-9 activities were enhanced (p<0.05), whereas both SAF (p<0.05) and FOL+SAF (p<0.05) prevented MMPs overactivation. The decidua from diabetic rats showed enhanced activity of MMP-2 and MMP-9 (p<0.001), SAF diminished MMP9 overactivity (p<0.05) and FOL+SAF reduced both MMP-2 and MMP-9 (p<0.01) overactivities. The elevated malformation rate in diabetic rats (p<0.001) was reduced with maternal treatments with FOL, SAF and FOL+SAF (p<0.05). Conclusions: In embryos and decidua from diabetic rats, FOL and SAF have the ability to reduce the malformation rate at least in part through the regulation of oxidative stress and MMPs overactivity.