title: Altered matrix metalloproteinases and tissue inhibitors of metalloproteinases in embryos from diabetic rats during early organogenesis.
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.
authors.affiliation: Laboratory of Reproduction and Metabolism, CEFYBO-CONICET, School of Medicine, University of Buenos Aires, Argentina. rominahiga@gmail.com
authors.forename: Romina
authors.initials: R
authors.lastname: Higa
authors.forename: Melisa
authors.initials: M
authors.lastname: Kurtz
authors.forename: Evangelina
authors.initials: E
authors.lastname: Capobianco
authors.forename: Nora
authors.initials: N
authors.lastname: Martínez
authors.forename: Verónica
authors.initials: V
authors.lastname: White
authors.forename: Alicia
authors.initials: A
authors.lastname: Jawerbaum
mesh_terms: D000818:Animals; D003656:Decidua / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism*; D005260:Female; D015227:Lipid Peroxidation; D020778:Matrix Metalloproteinase 2 / Q000032:analysis / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000032:analysis / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis; D038081:Organogenesis; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis / Q000378:metabolism; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000032:analysis / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000032:analysis / Q000378:metabolism*
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D019717:Tissue Inhibitor of Metalloproteinase-3; D019714:Tissue Inhibitor of Metalloproteinases; D019716:Tissue Inhibitor of Metalloproteinase-2; D009569:Nitric Oxide; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9