Matrix metalloproteinases-2 and -9 and their inhibitors are produced by the human 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 postulate that during the process of cervical ripening, there is an increase in the activity of MMP in order to facilitate cervical connective tissue change. We have previously demonstrated that nitric oxide (NO) donors induce cervical ripening in vivo. A secondary hypothesis is that NO donors regulate MMP activity within the human uterine cervix. Cervical tissue biopsies were obtained from both pregnant and non-pregnant subjects. Cervical fibroblasts were cultured from the non-pregnant tissue. MMP-2 was present in conditioned media from pregnant and non-pregnant cervical explants and non-pregnant cervical fibroblasts. MMP-9 secretion was only detected in explants from non-pregnant women. TIMP-1, -2 and -4 were released by all cervical explants and fibroblast preparations. Pregnant women, in the first trimester, were treated with an NO donor (isosorbide mononitrate) in vivo. Cervical explants and fibroblasts from non-pregnant women were treated with the NO donor spermine nonoate in vitro. Treatment with an NO donor either in vivo or in vitro had no effect on the secretion of the MMP or TIMP studied. Further studies evaluating the mechanisms involved in cervical ripening are required.