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

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

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  • 1Laboratory of Reproduction and Metabolism, CEFYBO-CONICET, School of Medicine, University of Buenos Aires, Argentina.


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.

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