Matrix Metalloproteinase-8 Correlates with the Cervical Ripening Process in Humans

Background: To determine levels of matrix metalloproteinases MMP-1, -3 and -8 and localize them and the tissue inhibitors of metalloproteinases TIMP-1 and -2 in human cervical tissue during the cervical ripening process.

Methods: Cervical biopsies were obtained from 10 term-pregnant (TP) women and from nine women immediately after vaginal delivery. Ten nonpregnant (NP) women served as controls. Levels of MMP-1, -3 and -8 were analyzed in supernatants of homogenized cervical tissue by specific enzyme-linked immunosorbent assay (EIA). Localization with immunohistochemistry of these MMPs and TIMP-1 and -2 was performed using monoclonal antibodies.

Results: MMP-8 reached its peak median level, 7300 ng/mg wet weight, in biopsies obtained from postpartum (PP) women, as compared to 86 ng/mg wet weight in NP (p<0.001) and 266 ng/mg wet weight in TP (p=0.016) women. The immunohistochemical results confirmed these findings, with a clear increase in MMP-8 staining in ripened cervix localized primarily in the stromal tissue. Levels of MMP-1 and -3 as measured with EIA were low in all three groups, but immunohistochemically a more frequent positive staining for MMP-1 and -3 was registered in pregnant cervical tissue compared to nonpregnant. For TIMP-1 and also for TIMP-2 immunohistochemical analysis showed that staining in all groups was more prominent in pregnant cervical tissue compared to nonpregnant.

Conclusion: The results indicate that MMP-8 is involved in the process of cervical ripening, and that MMP-1 and -3 and their inhibitors TIMP-1 and -2 may also play a role in this complicated process.