Ovarian tissue remodeling: role of matrix metalloproteinases and their inhibitors

Follicular formation, growth or atresia, and ovulation as well as luteal formation and subsequent regression are dependent upon cyclical remodeling of the extracellular matrix (ECM). The proteinaceous and nonproteinaceous components of the ECM provide the tissue specific, extracellular architecture to which cells attach. Furthermore, the ECM modulates cellular activities through cellular surface receptors and serves as a reservoir for specific growth factors, cytokines, and binding proteins. The ability of the ECM to direct the proliferation, differentiation and function of cells implicates ECM remodeling in normal ovarian function. Specific components of the ECM are cleaved by matrix metalloproteinases (MMPs) whose activities are specifically inhibited by tissue inhibitors of metalloproteinases (TIMPs). MMPs are zinc- and calcium-dependent enzymes that collectively degrade proteinaceous components of the ECM. Controlled turnover of ECM by MMPs and TIMPs may be essential for creating and (or) preserving microenvironments conducive to follicular and luteal function and is likely dependent upon the ratio of enzyme to inhibitor. To date, most studies have focused upon correlating ovarian expression of MMPs and TIMPs with various stages of the reproductive cycle. From these studies, many potential key regulators of ovarian ECM remodeling have been identified. This review presents evidence for the involvement of MMPs and TIMPs in ECM remodeling associated with follicular and luteal function.