title: Secretion of tissue inhibitors of matrix metalloproteinases by human fetal membranes, decidua and placenta at parturition.
abstract: At parturition, breakdown of extracellular matrix in the fetal membranes may play a part in the rupture of the membranes and in the aetiology of premature rupture, in addition to having a regulatory role in the cell-cell interactions and signalling at the feto-maternal interface to stimulate myometrial contractility. The matrix metalloproteinases (MMPs) are important enzymes for the breakdown of extracellular matrix and their activity is regulated by a family of endogenous inhibitors, the tissue inhibitors of matrix metalloproteinases (TIMPs). At parturition, alteration in the balance between MMPs and TIMPs may mediate this extracellular matrix breakdown during rupture of fetal membranes. The aims of this study were to determine if the intrauterine secretion of TIMPs changes at labour, and to characterise their cellular sources. A broad range of TIMP activities (27-30 kDa, 24 kDa and 21 kDa) were detected by reverse zymography in term amniotic fluid. There was a significant (P<0.05) decrease in the amount of TIMPs in amniotic fluid and their release with the onset of labour. The TIMPs were characterised by immunoblot as TIMPs-1, -2, -3 and -4. High levels of TIMPs were secreted by explants of chorio-decidua, decidua parietalis and placenta, with less being released by amnion. Immunolocalisation studies revealed a specific distribution pattern for each of the TIMP isoforms. Trophoblast cells of chorion laeve, decidua parietalis and placental syncytiotrophoblast demonstrated specific immunoreactivity for all four isoforms. TIMPs were also found bound to selective regions of extracellular matrix. The decrease in TIMPs during labour may permit increased breakdown of extracellular matrix in the fetal membranes and decidua at parturition, thus altering cell signalling at the feto-maternal interface and facilitating membrane rupture.
authors.affiliation: Department of Obstetrics and Gynaecology, Centre for Reproductive Biology, University of Edinburgh, Edinburgh, UK.
authors.forename: S C
authors.initials: SC
authors.lastname: Riley
authors.forename: R
authors.initials: R
authors.lastname: Leask
authors.forename: F C
authors.initials: FC
authors.lastname: Denison
authors.forename: K
authors.initials: K
authors.lastname: Wisely
authors.forename: A A
authors.initials: AA
authors.lastname: Calder
authors.forename: D C
authors.initials: DC
authors.lastname: Howe
mesh_terms: D000653:Amniotic Fluid / Q000737:chemistry; D046508:Culture Techniques; D003656:Decidua / Q000737:chemistry / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005321:Extraembryonic Membranes / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007743:Labor, Obstetric / Q000502:physiology*; D010920:Placenta / Q000737:chemistry / Q000378:metabolism*; D011247:Pregnancy; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis / Q000378:metabolism; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000032:analysis / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000032:analysis / Q000378:metabolism*; D000097792:Tissue Inhibitor of Metalloproteinase-4
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D019717:Tissue Inhibitor of Metalloproteinase-3; D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4