The role of nitric oxide on MMP2 and MMP9 in placenta and fetus from diabetic rats

PUSTOVRH CAROLINA; JAWERBAUM ALICIA; WHITE VERÓNICA; CAPOBIANCO EVANGELINA; HIGA ROMINA; LÓPEZ-COSTA JUAN JOSÉ; GONZÁLEZ, ELIDA

REPRODUCTION

SOCIETY FOR REPRODUCTION AND FERTILITY

Año: 2007 vol. 134 p. 605 - 613

1470-1626

Matrix metalloproteinases (MMPs) play an important role in the tissue remodelling that accompanies the rapid growth, differentiation and structural changes of the placenta and several fetal organs. In the present study we investigated whether the diabetic maternal environment may alter the regulatory homeostasis exerted by nitric oxide (NO) on MMPs activity in the feto-placental unit from rats at midgestation. We found that NADPH- diaphorase activity, which reflects the distribution and activity of NO synthases (NOS), was increased in both placenta and fetuses from diabetic rats when compared to controls. In addition, while a NO donor enhanced MMP-2 and MMP-9 activities, a NOS inhibitor reduced these activities in the maternal side of the placenta from control rats. This regulatory effect of NO was only observed on MMP-9 in the diabetic group. On the other hand, the NO donor did not modify MMP-2 and MMP-9 activities, while the NOS inhibitor reduced MMP-9 activity in the fetal side of both control and diabetic placentas. In the fetuses, MMP-2 was enhanced by the NO donor and reduced by the NO inhibitor in both fetuses from control and diabetic rats. Overall, this study demonstrates that NO is able to modulate the activation of MMPs in the feto-placental unit, and provides supportive evidence that increased NOS activity leads to NO overproduction in the feto-placental unit from diabetic rats, an alteration closely related to the observed MMPs dysregulation that may have profound implications in the formation and function of the placenta and the fetal organs.