Matrix metalloproteinases-2 and-9 and their inhibitors are produced by thehuman uterine cervix but their secretion is not regulated by nitric oxide donors

We have investigated the presence of matrix metalloproteinases (MMP)-2 and -9 and their tissue inhibitors (TIMP) in the human uterine cervix. We postu late that during the process of cervical ripening, there is an increase in the activity of MMP in order to facilitate cervical connective tissue chang e. We have previously demonstrated that nitric oxide (NO) donors induce cer vical ripening in vivo. A secondary hypothesis is that NO donors regulate M MP activity within the human uterine cervix. Cervical tissue biopsies were obtained from both pregnant and nonpregnant subjects. Cervical fibroblasts were cultured from the non-pregnant tissue. MMP-2 was present in conditione d media from pregnant and non-pregnant cervical explants and non-pregnant c ervical fibroblasts. MMP-9 secretion was only detected in explants from non -pregnant women. TIMP-1, -2 and -4 were released by all cervical explants a nd fibroblast preparations. Pregnant women, in the first trimester, were tr eated with an NO donor (isosorbide mononitrate) in vivo. Cervical explants and fibroblasts from non-pregnant women were treated with the NO donor sper mine nonoate in vitro. Treatment with an NO donor either in vivo or in vitr o had no effect on the secretion of the MMP or TIMP studied. Further studie s evaluating the mechanisms involved in cervical ripening are required.