Metalloproteinase 2 activity and modulation in uterus from neonatal streptozotocin-induced diabetic rats during embryo implantation

Matrix metalloproteinases (MMPs) are responsible for the remodelling of the uterine extracellular matrix during embryo implantation. Nitric oxide (NO) production is increased at the time when implantation begins. Abnormal tissue levels of MMPs are present in diabetes; elevated NO levels in tissues and an increased oxidative stress are also found. The present work evaluates the uterine MMP2 activity and levels during embryo implantation, as well as the influence of nitridergic compounds and reactive oxygen species (ROS) on the MMP2 enzymatic activity in a model of neonatal streptozotocin-induced diabetic rat. Metalloproteinase 2 activity and levels are increased in diabetic tissues compared with controls (P < 0.05 and P < 0.002 respectively). The uterine enzymatic activity in diabetic animals decreases in the presence of the NOS inhibitor NG-nitro-L-arginine methyl ester (P < 0.01) and is enhanced (P < 0.005) when a generating ROS system (xanthine/xanthine oxidase) is added to the incubating medium. It was also found that uterine superoxide dismutase activity is higher in diabetic rats than in control rats on the day of implantation (P < 0.001), suggesting a compensatory antioxidant ability. In conclusion, the results show that the uterine MMP2 activity, which is higher in diabetic animals than in control animals, is modulated positively by NO and ROS during embryo implantation in a model of streptozotocin-induced diabetic rats.