Presence of Four Tissue Inhibitors of Matrix Metalloproteinases (TIMP‐1, −2, −3 and −4) in Human Fetal Membranes

PROBLEM: Matrix metalloproteinases play a critical role in fetal membrane extracellular matrix (ECM) homeostasis. Remodeling of the ECM during normal placental development is a balanced activity between various matrix metalloproteinases and their tissue‐specific counter‐ regulatory proteins (tissue inhibitors of matrix metalloproteinases [TIMPs]). We have reported the presence of TIMP‐1 and TIMP‐2 in placental membranes in culture. In this study we have investigated the membrane expression of TIMP‐1 and TIMP‐2 during labor and nonlabor conditions and also the presence of two novel TIMP family members (TIMP‐3 and TIMP‐4). METHOD OF STUDY: Amniochorionic membranes collected from women undergoing Cesarean section and were cultured in an organ explant system. Membranes were also collected from laboring women after vaginal delivery. Samples were subjected to reverse transcriptase‐polymerase chain reaction (RT‐PCR) using primers specific for TIMP‐1, TIMP‐2, TIMP‐3, and TIMP‐4. Localization of TIMP mRNAs was accomplished by in situ hybridization, and peptides were localized by immunocytochemistry. RESULTS: RT‐PCR data demonstrated the expression of all the TIMPs in tissues from laboring and nonlaboring women as well as in cultured membranes. TIMP‐4 expression was seen in RT‐PCR, however, only a faint band was visible in all the tissues tested. In situ hybridization localized the TIMP mRNAs to the amnion, chorion, and to scattered cells in the connective tissue. CONCLUSION: Human fetal membrane cells (amniochorion and decidua) express mRNA for all the TIMPs studied so far.