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.


CONCLUSIONS
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.
Sennström
Maria B
MB
Department of Women and Child Health, Division for Obstetrics and Gynecology, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden. maria.sennstrom@ks.se
Brauner
Annelie
A
Byström
Birgitta
B
Malmström
Anders
A
Ekman
Gunvor
G
D000328:Adult; D016022:Case-Control Studies; D020070:Cervical Ripening / Q000378:metabolism*; D002584:Cervix Uteri / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism; D008666:Metalloendopeptidases / Q000378:metabolism*; D008875:Middle Aged; D011247:Pregnancy; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism
D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D020784:Matrix Metalloproteinase 8; D020781:Matrix Metalloproteinase 1