title: Oxidative stress promotes the increase of matrix metalloproteinases-2 and -9 activities in the feto-placental unit of diabetic rats.
abstract: Maternal diabetes increases the risk of congenital malformations, placental dysfunction and diseases in both the neonate and the offspring's later life. Oxidative stress has been involved in the etiology of these abnormalities. Matrix metalloproteases (MMPs), involved in multiple developmental pathways, are increased in the fetus and placenta from diabetic experimental models. As oxidants could be involved in the activation of latent MMPs, we investigated a putative relationship between MMPs activities and oxidative stress in the feto-placental unit of diabetic rats at midgestation. We found that H2O2 enhanced and that superoxide dismutase (SOD) reduced MMPs activities in the maternal side of the placenta and in the fetuses from control and diabetic rats. MMPs were not modified by oxidative status in the fetal side of the placenta. Lipid peroxidation was enhanced in the maternal and fetal sides of the placenta and in the fetus from diabetic rats when compared to controls, and gradually decreased from the maternal placental side to the fetus in diabetic animals. The activities of the antioxidant enzymes SOD and catalase were decreased in the maternal placental side, catalase activity was enhanced in the fetal placental side and both enzymes were increased in the fetuses from diabetic rats when compared to controls. Our data demonstrate changes in the oxidative balance and capability of oxidants to upregulate MMPs activity in the feto-placental unit from diabetic rats, a basis to elucidate links between oxidative stress and alterations in the developmental pathways in which MMPs are involved.
authors.affiliation: Laboratorio de Reproducción y Metabolismo, Centro de Estudios Farmacológicos y Botánicos (CEFYBO-CONICET), Buenos Aires, Argentina.
authors.forename: María Carolina
authors.initials: MC
authors.lastname: Pustovrh
authors.forename: Alicia
authors.initials: A
authors.lastname: Jawerbaum
authors.forename: Evangelina
authors.initials: E
authors.lastname: Capobianco
authors.forename: Verónica
authors.initials: V
authors.lastname: White
authors.forename: Nora
authors.initials: N
authors.lastname: Martínez
authors.forename: Juan José
authors.initials: JJ
authors.lastname: López-Costa
authors.forename: Elida
authors.initials: E
authors.lastname: González
mesh_terms: D000818:Animals; D002374:Catalase / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000201:enzymology / Q000378:metabolism*; D015227:Lipid Peroxidation; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D018384:Oxidative Stress; D010920:Placenta / Q000201:enzymology / Q000378:metabolism*; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000201:enzymology / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D017382:Reactive Oxygen Species; D002374:Catalase; D013482:Superoxide Dismutase; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9