Increased metalloproteinases in fetoplacental unit of diabetic rats at midgestation: involvement of reactive oxygen species

GONZÁLEZ ELIDA; PUSTOVRH CAROLINA; LÓPEZ COSTA JUAN JOSÉ; CAPOBIANCO EVANGELINA; WHITE VERÓNICA; MARTÍNEZ NORA; JAWERBAUM ALICIA

Luso, Coimbra,

Congreso; Third Scientific Meeting, 36th Annual Meeting, Diabetes and Pregnancy Study Group. EASD.; 2004

Diabetes and Pregnancy Study Group. EASD.

Matrix metalloproteinases (MMPs) are mayor regulators of extracellular matrix remodelling during placental and fetal development. Reactive oxygen species (ROS) are involved in the cleavage of the MMPs proenzymes leading to the formation of enzymes with biological activity. Hyperglycemia is responsible of an enhanced production of ROS and of abnormal levels of MMPs in different cell types. In order to determine whether the diabetic milieu induces alterations in the oxidative state and in MMPs levels and regulation in the fetoplacental unit during rat midpregnancy, we evaluated a) MMP-2 and MMP-9 activities (zymography) and distribution (inmunohistochemistry) as well as b) lipid peroxidation and the influence of ROS on MMPs activity in the placenta (maternal and fetal side) and fetus from controls (C) and neonatal-streptozotocin-induced diabetic (n-STZ) rats at midgestation. In the placenta of n-STZ diabetic rats a stronger expression of MMPs was detected (p<0.01) in comparison to controls. Placental MMP-2 and MMP-9 activities from diabetic animals were higher than those found in the control group (p<0.01). MMP-9 activity was absent both in C and n-STZ fetuses, while fetal MMP-2 activity was higher in diabetic tissues than in C (p<0.05). Hydrogen peroxide and superoxide dismutase additions to fetal and decidual explants produced respectively an enhancement (p<0.01) and a decrease (p<0.05) of MMP-2 and MMP-9 activities, while no changes could be observed in the fetal side of the placenta. On the other hand, an increased production of lipid peroxideswas detected in the fetal side (p<0.05) and in the fetus (p<0.02) from n-STZ animalscompared to C, while placental TBARs content was equal in the maternal side from control and diabetic rats. We conclude that placental and fetal MMPs activities are higher in n-STZ than in C animals, an enhancement that is likely to be influenced by high levels of ROS. Our results also suggest that the decidua is able to compensate the oxidative stress induced by maternal hyperglycemia, but do not constitute an effective barrier against ROS, which are elevated and affect both the placental fetal side and the developing fetus.