Document Detail

Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-3 are key regulators of extracellular matrix degradation by mouse embryos.
MedLine Citation:
PMID:  11319136     Owner:  NLM     Status:  MEDLINE    
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.
E J Whiteside; M M Jackson; A C Herington; D R Edwards; M B Harvey
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biology of reproduction     Volume:  64     ISSN:  0006-3363     ISO Abbreviation:  Biol. Reprod.     Publication Date:  2001 May 
Date Detail:
Created Date:  2001-04-25     Completed Date:  2001-08-16     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0207224     Medline TA:  Biol Reprod     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1331-7     Citation Subset:  IM    
Centre for Molecular Biotechnology, School of Life Sciences, Queensland University of Technology, Brisbane, Queensland 4001, Australia.
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MeSH Terms
Blastocyst / physiology,  ultrastructure
Cell Line
Culture Media, Conditioned
Culture Techniques
Embryo Implantation
Embryo, Mammalian / physiology,  ultrastructure*
Enzyme Inhibitors
Extracellular Matrix / metabolism*
Matrix Metalloproteinase 9 / antagonists & inhibitors,  physiology*
Oligonucleotides / pharmacology
Oligonucleotides, Antisense / pharmacology
Tissue Inhibitor of Metalloproteinase-3 / physiology*
Reg. No./Substance:
0/Culture Media, Conditioned; 0/Enzyme Inhibitors; 0/Oligonucleotides; 0/Oligonucleotides, Antisense; 0/Tissue Inhibitor of Metalloproteinase-3; EC Metalloproteinase 9

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