Increased matrix metalloproteinases 2 and 9 in placenta of diabetic rats at midgestation.
Matrix metalloproteinases (MMPs) are involved in placental remodelling throughout pregnancy. Diabetes mellitus induces alterations in tissue production of NO, a regulator of MMPs activity. The present work evaluates placental and fetal MMPs and NO levels during midpregnancy in neonatal streptozotocin-induced diabetic rats. MMP-2 and MMP-9 immunolabelling was increased both in the labyrinth zone (p<0.001) and in the giant trophoblast cells of the junctional zone (p<0.001) from diabetic placenta, when compared with controls. Also MMP-2 (p<0.01) and MMP-9 (p<0.005) activities were increased in both maternal and fetal sides of diabetic placenta when related to controls. In both sides of the diabetic placenta, nitrate/nitrite concentrations (which indicate NO production) were higher than in controls (p<0.05). An intense immunostaining for nitrotyrosine, indicating peroxynitrite-induced damage, was found in both labyrinth (p<0.001) and junctional zones (p<0.001) of diabetic placenta. Enhanced MMP-2 activity (p<0.05) and NO production were also higher in the fetuses from diabetic rats when compared to controls (p<0.005). These findings demonstrate alterations in MMPs and NO in the feto-placental unit of diabetic rats, anomalies that are likely to be involved in the developmental alterations induced by maternal diabetes.
Pustovrh
M C
MC
Laboratory of Reproduction and Metabolism, Centro de Estudios Farmacológicos y Botánicos, Serrano 669 (C1414DEM), Buenos Aires, Argentina.
Jawerbaum
A
A
Capobianco
E
E
White
V
V
López-Costa
J J
JJ
González
E
E
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000378:metabolism*; D005260:Female; D005865:Gestational Age; D007150:Immunohistochemistry; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D010920:Placenta / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism
D009566:Nitrates; D009573:Nitrites; C002744:3-nitrotyrosine; D014443:Tyrosine; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9