Matrix metalloproteinases-2 and-9 in the human uterine cervix during midcyclic cervical opening

Objective: Midcyclic cervical dilatation in its basic mechanisms is thought to resemble cervical dilatation during parturition, where an infiltration of the cervical stroma and the activation of matrix metalloproteinases is known to play an important role. In this study we have investigated the presence and localization of matrix metalloproteinases (MMP)-2 and -9 in the human uterine cervix across the menstrual cycle. Methods: Samples of tissue from human uterine cervix were obtained from specimens from 14 premenopausal patients undergoing hysterectomy (6 were removed during follicular phase [day 1 - 11], 4 in the periovulatory phase [day 12 - 16], 4 in the secretory phase [day 17-28]). Paraffin embedded slides were stained with a monoclonal antibody against MMP 2 and MMP 9. The relative intensity of the staining reaction was described by two independent researchers and classified in semiquantitative categories (- negative; + faint; + + moderate; +++ strong). Results: MMP 9 was immunolocalized in different cellular compartments of the tissue: glandular epithelium, vascular endothelium, stroma and macrophages. An increase of MMP 9 was detected only in glandular epithelium during periovulatory phase. In vascular endothelium and macrophages MMP 9 was present in all phases of the menstrual cycle in an equal intensity of staining reaction. MMP 2 was immunolocalized in the glandular epithelium of the follicular and secretory phase in a moderate intensity, while the cervical stroma showed only a faint staining reaction for MMP 2. Conclusion: The finding of an increase of MMP 9 in glandular epithelium during periovulatory phase is consistent with the involvement of MMP 9 in the mechanisms of midcyclic cervical dilatation. At the same time the rather unspecific expression of MMP 2 and MMP 9 in all phases of the menstrual cycle indicates that midcyclic cervical dilatation may depend on the involvement of several, hormonally regulated mediators. Further studies evaluating the mechanisms are required.