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

PUSTOVRH MC, JAWERBAUM A, WHITE V, CAPOBIANCO E, HIGA R, MARTÍNEZ N, LÓPEZ-COSTA JJ, GONZÁLEZ E

REPRODUCTION

Bioscientifica

Lugar: UK; Año: 2007 vol. 134 p. 605 - 613

1470-1626

Matrix metalloproteinases (MMPs) play an important role in tissue remodeling 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 thatNADPH-diaphorase activity,which reflects the distributionand activity ofNOsynthases (NOS),was increased in both placenta and fetuses from diabetic rats when compared with controls. In addition, while a NO donor enhanced MMP2 and MMP9 activities, a NOS inhibitor reduced these activities in thematernal side of the placenta from control rats. This regulatory effect ofNOwas only observed onMMP9 in the diabetic group.Onthe other hand, the NO donor did no tmodify MMP2 and MMP9 activities, while the NOS inhibitor reduced MMP9 activity in the fetal side of both control and diabetic placentas. In the fetuses, MMP2 was enhanced by theNO donor and reduced by theNO inhibitor in both fetuses from control and diabetic rats. Overall, this study demonstrates that NO is able tomodulate the activation of MMPs in the fetoplacental 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.