Secretion of tissue inhibitors of matrix metalloproteinases by human fetalmembranes, decidua and placenta at parturition

At parturition, breakdown of extracellular matrix in the fetal membranes ma y play a part in the rupture of the membranes and in the aetiology of prema ture rupture, in addition to having a regulatory role in the cell-cell inte ractions and signalling at the feto-maternal interface to stimulate myometr ial contractility. The matrix metalloproteinases (MMPs) are important enzym es for the breakdown of extracellular matrix and their activity is regulate d by a family of endogenous inhibitors, the tissue inhibitors of matrix met alloproteinases (TIMPs). At paturition, alteration in the balance between M MPs and TIMPs may mediate this extracellular matrix breakdown during ruptur e of fetal membranes. The aims of this study were to determine if the intra uterine secretion of TIMPs changes at labour, and to characterise their cel lular sources. A broad range of TIMP activities (27-30 kDa, 24 kDa and 21 k Da) 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 im munoblot as TIMPs-1, -2, -3 and -4. High levels of TIMPs were secreted by e xplants of chorio-decidua, decidua parietalis and placenta, with less being released by amnion. Immunolocalisation studies revealed a specific distrib ution pattern for each of the TIMP isoforms. Trophoblast cells of chorion l aeve, decidua parietalis and placental syncytiotrophoblast demonstrated spe cific immunoreactivity for all four isoforms. TIMPs were also found bound t o selective regions of extracellular matrix. The decrease in TIMPs during l abour may permit increased breakdown of extracellular matrix in the fetal m embranes and decidua at parturition, thus altering cell signalling at the f eto-maternal interface and facilitating membrane rupture.