Alterations in the activities of matrix metalloproteinases and their tissular inhibitors in the decidua from diabetic rats.

HIGA R; PUSTOVRH C; WHITE V; GONZÁLEZ E; JAWERBAUM A

Los Cocos, Córdoba

Simposio; III Latin American Symposium on Maternal Fetal Interaction and Placenta: Basic & Clinical Research.; 2007

Asociación Latinoamericana de estudio de la Interacción Materno Fetal y la placenta

Localized proteolytic degradation of the extracellular matrix in the decidua allows its remodeling during gestation and has profound effects on signals reaching the developing embryo and placenta. Matrix metalloproteinases  (MMPs) 2 and 9 are involved in these remodeling processes. They are synthesized as proenzymes, cleaved to become active, and their activity is regulated by tissue inhibitors of matrix metalloproteinases (TIMPs), which directly interact with their active site. The aim of the present work was to analyze the levels of MMP2, MMP9 and their proenzymes, as well as the levels of TIMP 3 in the deciduas obtained from control (C) and diabetic (D) rats on day 10.5 of pregnancy, a stage corresponding to early embryo organogenesis.  Methods: Diabetes was induced by streptozotocin administration (50 mg/kg) to adult rats. Decidual levels of MMP2 and MMP9 and their proenzymes were evaluated by zymography. Decidual levels of TIMP3 were analyzed by reverse zymography. Results: MMP9 was found mainly in its activated form in deciduas from C and D rats, and its activity was enhanced in D (92%, p<0.05) when compared to C. MMP2 was found mainly in its proenzyme form in deciduas from C and D rats, and its levels were increased in  D (84%, p<0.01) when compared to C. The levels of TIMP3 were increased in D deciduas in its glycosylated (35%, p<0.01) and non-glycosilated (68%, p<0.01) forms when compared to C. Conclusions: Our results showed an enhanced activation of MMP9 and increased levels of proMMP2 in decidual tissue from diabetic rats that may lead to an abnormal remodeling process during early embryo organogenesis and placentation. This alteration may be in part compensated by increased levels of TIMP3.