Molecular Human Reproduction, Vol. 9, No. 3, 143-149,
March 2003
© 2003 European Society of Human Reproduction and Embryology
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Expression and implications of tissue inhibitor of metalloproteinases-4 in mouse embryo
Submitted on July 19, 2002; resubmitted on October 31, 2002. accepted on November 26, 2002
1 State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100080, People’s Republic of China and 2 Department of Chemistry and Biochemistry and Institute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306, USA
3 To whom correspondence should be addressed. e-mail: duane{at}panda.ioz.ac.cn
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.
Key words: blastocyst/implantation/matrix metalloproteinases/mouse embryo/TIMP-4
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