Cellular turnover and extracellular matrix remodeling in female reproductive tissues: functions of metalloproteinases and their inhibitors

Female reproductive tissues possess a unique ability to accommodate a remar kable amount of cell turnover and extracellular matrix (ECM) remodeling fol lowing puberty. Cellular structures within ovary, uterus, and mammary tissu e not only change cyclically in response to ovarian hormones but also under go differentiation during pregnancy, and eventually revert to that resembli ng the pre-pregnant stage. Cell proliferation, apoptosis, invasion, and dif ferentiation are integral cellular processes that are precisely regulated i n reproductive tissues, but become dysregulated in pathologies such as canc er. Explicit reorganization of ECM and basement membranes is also critical to preserve the form and function of these tissues. Here we review the evid ence that coordinated spatiotemporal expression patterns of matrix metallop roteinase (MMP) genes and their tissue inhibitors (TIMPs) are important in cell and ECM turnover of the ovary, uterus, and mammary tissues. We discuss how perturbation in these gene families may impact the biology of these re productive tissues and the factors implicated in the control of MMP and TIM P gene expression. The observed trends in MMP and TIMP expression involved in ovarian and mammary carcinomas are also presented.