Altered matrix metalloproteinases and tissue inhibitors of metalloproteinases in embryos from diabetic rats during early organogenesis

Romina Higa; Melisa Kurtz; Evangelina Capobianco; Nora Martínez; Verónica White; Alicia Jawerbaum

doi:10.1016/j.reprotox.2011.09.003

Altered matrix metalloproteinases and tissue inhibitors of metalloproteinases in embryos from diabetic rats during early organogenesis

Reprod Toxicol. 2011 Dec;32(4):449-62. doi: 10.1016/j.reprotox.2011.09.003. Epub 2011 Sep 24.

Authors

Romina Higa¹, Melisa Kurtz, Evangelina Capobianco, Nora Martínez, Verónica White, Alicia Jawerbaum

Affiliation

¹ Laboratory of Reproduction and Metabolism, CEFYBO-CONICET, School of Medicine, University of Buenos Aires, Argentina. rominahiga@gmail.com

PMID: 21963884
DOI: 10.1016/j.reprotox.2011.09.003

Abstract

Maternal diabetes increases the risks for embryo malformations. Matrix metalloproteinase-2 (MMP-2) and MMP-9 are two relevant MMPs for embryo development. Here, we addressed whether changes in these MMPs and in tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and TIMP-2 are altered in embryos and decidua from type 1 diabetic rats during early organogenesis. Our results demonstrate MMP-2 and MMP-9 overactivities and overexpression, together with increases in lipid peroxidation and nitric oxide production in embryos and decidua from diabetic animals. There is a concomitant increase in the inhibitory activity of TIMP-1 and TIMP-2 in embryos and decidua, and an increase in protein expression of embryonic TIMP-1 and TIMP-2. In situ zymography demonstrated MMPs overactivities despite increased TIMPs in embryos and decidua in maternal diabetes during early organogenesis. This study reveals that maternal diabetes leads to profound alterations in MMPs/TIMPs balance during embryo organogenesis, the gestational period during which most malformations are induced.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Decidua / chemistry
Decidua / enzymology
Decidua / metabolism
Diabetes Mellitus, Experimental / metabolism*
Embryo, Mammalian / chemistry
Embryo, Mammalian / enzymology
Embryo, Mammalian / metabolism*
Female
Lipid Peroxidation
Matrix Metalloproteinase 2 / analysis
Matrix Metalloproteinase 2 / metabolism
Matrix Metalloproteinase 9 / analysis
Matrix Metalloproteinase 9 / metabolism
Matrix Metalloproteinases / analysis
Matrix Metalloproteinases / metabolism*
Nitric Oxide / biosynthesis
Organogenesis*
Pregnancy
Pregnancy in Diabetics / metabolism*
Rats
Rats, Wistar
Tissue Inhibitor of Metalloproteinase-1 / analysis
Tissue Inhibitor of Metalloproteinase-1 / metabolism
Tissue Inhibitor of Metalloproteinase-2 / analysis
Tissue Inhibitor of Metalloproteinase-2 / metabolism
Tissue Inhibitor of Metalloproteinase-3 / analysis
Tissue Inhibitor of Metalloproteinase-3 / metabolism
Tissue Inhibitor of Metalloproteinases / analysis
Tissue Inhibitor of Metalloproteinases / metabolism*

Substances

Tissue Inhibitor of Metalloproteinase-1
Tissue Inhibitor of Metalloproteinase-3
Tissue Inhibitor of Metalloproteinases
Tissue Inhibitor of Metalloproteinase-2
Nitric Oxide
Matrix Metalloproteinases
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9