Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-3 are key regulators of extracellular matrix degradation by mouse embryos

Edwards, Dylan, Harvey, Mark, Herington, Adrian, Jackson, Michael, & Whiteside, Eliza (2001) Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-3 are key regulators of extracellular matrix degradation by mouse embryos. Biology of Reproduction, 64(5), pp. 1331-1337.

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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.

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ID Code: 21751
Item Type: Journal Article
Refereed: Yes
Additional Information: Articles free to read on journal website after 12 months
Keywords: Embryo implantation, extracellular matrix, Matrix metalloproteinase 9 (MMP-9)
DOI: 10.1095/biolreprod64.5.1331
ISSN: 0006-3363
Divisions: Past > QUT Faculties & Divisions > Faculty of Science and Technology
Deposited On: 17 Jun 2009 12:57
Last Modified: 27 Jan 2015 02:28

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