The Effect Of Mifepristone On The Expression Of MMP-9 And TIMP-1 In Human Villus And Deciduas Of Early Pregnancy

Objective: To study the localization and expression of matrix metalloproteinase-9(MMP-9) and tissue Inhibitor of metalloproteinase-1(TIMP-1) in the villus and deciduas of early pregnancy and whether such expression was altered after different dose of mifepristone treatments. Investigated the role of MMP-9/TIMP-1 in the mechanism of antigestational action of mifepristone, and the relationship between MMP-9 / TIMP-1 and normal early pregnancy.Methods: Sixty patients who required termination of early pregnancy were randomly separated into four groups according to different treatments: 1.the control group with no mifepristone treament; 2. 50mg-mifepristone treatment group; 3. 100mg-mifepristone treatment group; 4. 150mg-mifepristone treatment group, and 15 for each group. After 48 hours the villus, deciduas were obtained through artifical abortion. Apply immunohistochemistry technology and computer image analysis systems to analysis the localization and expression of MMP-9 and TIMP-1 in the villus and deciduas of early pregnancy.Results:1. MMP-9 and TIMP-1 exhibited positive staining was obviously appeared mainly at the trophoblast and capillary endothelial cell of the villus, decidual cell, glandular epithelium cell and vascular endothelial cell of deciduous.2.The expression of MMP-9 and TIMP-1 in the villus and deciduas of the control group and the mifepristone treated groups.2.1 The villus of the mifepristone treated groups expressed higher level of MMP-9, lower level of TIMP-1 and higher ratio of MMP-9/TIMP-1 than that of the control group (P<0.01). There were no significant difference in the expression of MMP-9 and TIMP-1 in villus of the mifepristone treated group(sP >0.05). The ratio of MMP-9/TIMP-1 in villus of the mifepristone treated groups and the dose of mifepristone were correlated positively(P <0.05).2.2 The deciduas of the mifepristone treated groups expressed higher level of MMP-9, lower level of TIMP-1 and higher ratio of MMP-9/TIMP-1 than that of the control group (P <0.01). The MMP-9 expression of the 150mg-mifepristone treatment group was higher than the 50mg- and 100mg-mifepristone treatment groups (P <0.05), but there was no significant difference between the 50mg- and 100mg-mifepristone treatment groups(P >0.05). The expression of TIMP-1 and the dose of mifepristone were correlated negatively (P <0.01). The ratio of MMP-9/TIMP-1 in villus of the mifepristone treated groups and the dose of mifepristone were correlated positively.Conclusion:1.Mifepristone can influence the expression of MMP-9 and TIMP-1 in human villus and deciduous of early pregnancy, MMP-9 expression increased and TIMP-1 expression decreased. All the steps result in the degeneration and shedding of deciduas and the denudation of villus.2.The ratio of MMP-9/TIMP-1 in the villus and deciduous of the mifepristone treated groups are all higher than the control group, the ratio and the dose of mifepristone were correlated positively, which explain the balance of MMP-9 and TIMP-1 play an important role for sustaining the normal early pregnancy.