Study On The Relationship Between The Expressions Of MMP-9/TIMP-3 In Endometrium And Embryo Implantation

Objective: To explore the relationship between the expressions of matrix metalloproteinase-9 (MMP-9)/ tissue inhibitors of metalloproteinase-3(TIMP-3) in endometrium and embryo implantation.Methods: (1)Immunhistochemstry and pathologic image semi-quantification analysis were used to detect the expressions of MMP-9/TIMP-3 in endometria of selected cases, which are samples of normal women's endometria in proliferative and secretive phase, endometria in secretive phase of infertility, repetitive failure of IVF-ET treatment and habitual early abortion, and deciduavera of artificial abortion and medicinal abortion caused by mifepristone. (2)Mouse models of controlled ovarian hyperstimulation(COH) and luteal supporting by human chorionic gonadotropin (hCG) or progesterone(P) were used, and murine pre-implantation endometria were obtained, the same methods mentioned above was used to detect the expressions of MMP-9/TIMP-3 in the murine endometria.Results: (1)The endometria had the expressions of MMP-9/TIMP-3 in different phases of menstrual cycle, MMP-9/TIMP-3 expressed low in proliferative phase, but obvious high in secretive phase. (2) The expression of MMP-9 decreased obviously in the secretive phase endometria in the women with idiopathic infertility and with repetitive IVF-ET treatment, but the expression of TIMP-3 was normal. (3)The high expression of MMP-9 in secretive phase endometria was found in habitual early abortion cases. (4)MMP-9/TIMP-3 expressed strongly in deciduavera tissues, especially in stromal cells. (5)In the deciduavera tissues obtained from the abortion cases caused by mifepristone , the expression of MMP-9 decreased while TIMP-3 increased. (6)In the animal experiments, after using COH and luteal supporting protocol with hCG / P, the expression of MMP-9 in murine pre-implantation endometria reduced obviously while that of TIMP-3 increased oddly, and the abnormal morphology of murine uterus and endometrium were found. Conclusions: (1) The high expression of MMP-9/TIMP-3 in endometrium of secretive phase may be helpful to embryo implantation. (2) The low expression of MMP-9 in secretive phase endometrium may be the cause of idiopathic infertility and repetitive failure of IVF-ET treatment. (3) The balance of MMP-9 and TIMP-3 is blocked by the excessive expression of MMP-9 in secretive phase endometrium, which might be one of cause of habitual early abortion. (4) One of the mechanism of mifepristone inducing abortion might be that mifepristone increases the expression of MMP-9 and decreases that of TIMP-3. (5)The abnormal morphology of murine uterus and endometrium and the abnormal expressions of MMP-9/TIMP-3 in mouse endometrium, which induced by COH and luteal supporting protocol with hCG / P, may be harmful to mouse embryo implantation.