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1 May 2001 Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-3 Are Key Regulators of Extracellular Matrix Degradation by Mouse Embryos
Eliza J. Whiteside, Michael M. Jackson, Adrian C. Herington, Dylan R. Edwards, Mark B. Harvey
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Abstract

Embryo implantation in humans and rodents is a highly invasive yet tightly controlled process involving extracellular matrix (ECM) degradation. Matrix metalloproteinase 9 (MMP-9) has been implicated as the major facilitator of this ECM degradation. MMP-9 is expressed by the embryo's trophoblast cells, whereas tissue inhibitor of metalloproteinases 3 (TIMP-3) is expressed by the maternal uterine cells immediately adjacent to the trophoblast. We examined the functional roles of MMP-9 and TIMP-3 during in vitro ECM degradation by mouse embryos. Blastocysts were treated with either MMP-9 antisense or sense oligonucleotides and incubated on an ECM gel. The extent of ECM degradation exhibited by the blastocysts due to proteinase secretion was quantified. Embryos exposed to MMP-9 antisense oligonucleotides exhibited reduced ECM-degrading activity as compared with controls, and this reduced activity was correlated with the level of MMP-9 secreted by the embryos. The functional role of TIMP-3 was then examined by incubating blastocysts on an ECM gel that had been impregnated with various amounts of TIMP-3. In a dose-dependent manner, increases in TIMP-3 resulted in a reduction in ECM degradation and were correlated with diminished MMP-9 activity. These results provide important functional evidence that in vitro ECM degradation is regulated by embryo-derived MMP-9 and ECM-derived TIMP-3.

Eliza J. Whiteside, Michael M. Jackson, Adrian C. Herington, Dylan R. Edwards, and Mark B. Harvey "Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-3 Are Key Regulators of Extracellular Matrix Degradation by Mouse Embryos," Biology of Reproduction 64(5), 1331-1337, (1 May 2001). https://doi.org/10.1095/biolreprod64.5.1331
Received: 25 October 1999; Accepted: 1 December 2000; Published: 1 May 2001
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