title: Expression and implications of tissue inhibitor of metalloproteinases-4 in mouse embryo.
abstract: Matrix metalloproteinases (MMP), tissue inhibitors of metalloproteinases (TIMP), and MMP-TIMP interactions may contribute to the highly programmed process of embryo implantation. The loss of the delicate MMP-TIMP balance may lead to abnormal implantation. The role of TIMP-4 in mouse implantation has not been reported. This study examined mRNA and protein expression levels of TIMP-4 in the blastocyst and uteri of pregnant mice. We also investigated the effects of a specific TIMP-4 antibody on embryo outgrowth and on the gene and protein expression levels of two gelatinases. High levels of TIMP-4 mRNA and protein were detected in day 3-5 embryos and in the trophoblast cells of mice blastocysts, suggesting that TIMP-4 may be involved in embryo implantation. Furthermore, TIMP-4 antibody promoted blastocyst outgrowth in a dose-dependent manner, but had no effect on blastocyst adhesion to extracellular matrix. A specific TIMP-4 antibody also increased mRNA and protein expression levels and the enzymatic activities of gelatinase A (MMP-2) and gelatinase B (MMP-9). This study suggests that TIMP-4 may restrict mouse blastocyst outgrowth and embryo implantation by inhibiting the activities of MMP-2 and -9.
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100080, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Yun-Ge
authors.initials: YG
authors.lastname: Zhao
authors.forename: Yu-Jing
authors.initials: YJ
authors.lastname: Cao
authors.forename: Qing-Xiang Amy
authors.initials: QX
authors.lastname: Sang
authors.forename: En-Kui
authors.initials: EK
authors.lastname: Duan
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D010064:Embryo Implantation / Q000502:physiology; D004622:Embryo, Mammalian / Q000166:cytology / Q000502:physiology*; D005260:Female; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000235:genetics / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D010920:Placenta / Q000166:cytology / Q000378:metabolism; D011247:Pregnancy; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D019714:Tissue Inhibitor of Metalloproteinases; D014599:Uterus / Q000378:metabolism; D000097792:Tissue Inhibitor of Metalloproteinase-4
chemical_list: D039302:Integrin alphaVbeta3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D011506:Proteins; D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4