Differential activity of the gelatinases (matrix metalloproteinases 2 and 9) in the fetal membranes and decidua, associated with labour

Abstract

Degradation of the extracellular matrix in fetal membranes has been implicated in the rupture of fetal membranes, the process of parturition and placental detachment from the decidua after parturition. In this study we assessed labour-associated changes in gelatinase activity in cultured human amnion, chorion and decidua, as well as in amniotic fluid. We found that in media conditioned by decidua, following the establishment of uterine contractions, matrix metalloproteinase-2 (MMP-2) activity is increased while the protein tissue inhibitors of matrix metalloproteinase-1 (TIMP-1) level is decreased. The formation of a 130 kDa gelatinase band was also significantly increased after contractions began. In media conditioned by chorion, the initiation of uterine contractions did not change MMP activity or TIMP-1 levels. However, an increase in MMP-9 activity and a decrease in TIMP-1 protein levels were observed following the establishment of uterine contractions in media conditioned by amnion. We suggest that this differential spatial regulation provides a form for modulatory hieratical activity of the MMPs in the onset of labour allowing rupture of the membranes while avoiding premature placental separation.

Matrix metalloproteinases-2, -3 and tissue inhibitors of metalloproteinases-1, -2 in placentas from preterm pregnancies and their association with one-carbon metabolites

“…All the four TIMPs inhibit MMPs but differ in their affinities for different inhibitor-protease pairs (Brew & Nagase 2010). A number of studies have examined the levels of TIMP1 and TIMP2 in the amniotic fluid and fetal membranes both in term and preterm pregnancy (Athayde et al 1999, Fortunato et al 1999a, Maymon et al 2001, Goldman et al 2003. However, the results are inconsistent.…”

“…It is known that TIMP1 is a multifunctional protein and MMP inhibition is just one of its many properties (Hayakawa 1994). TIMPs also have biological activities that are independent of metalloproteinases; these include effects on cell growth and differentiation, cell migration, anti-angiogenesis, anti-and pro-apoptosis, and synaptic plasticity (Goldman et al 2003).…”

“…A number of factors are known to increase the risk of preterm birth, but the mechanisms underlying the initiation of preterm labor are not clear (Goldenberg et al 2008). Matrix metalloproteinases (MMPs) are reported to contribute during pregnancy in extracellular matrix (ECM) remodeling/degradation leading to cervical ripening, fetal membrane rupture, and finally placental separation from maternal uterus (Stygar et al 2002, Goldman et al 2003. Under physiological conditions, the activities of MMPs are regulated at the levels of transcription, by zymogen activation and inhibition by tissue inhibitors of metalloproteinases (TIMPs; Brew & Nagase 2010).…”

Anti-GalNAcβ: A novel anti-glycan autoantibody associated with pregnancy loss in women with antiphospholipid syndrome and in a mouse experimental model

“…Matrigel invasion assay was performed as previously described in the literature [27], using at JAR (HTB 144, ATCC) human choriocarcinoma cell line, in the presence and absence of anti-GalNAc-b, anti-b 2 GPI, anti-GalNAc-b (control aGA) and control IgG at different concentrations. Evaluation of cell proliferation within the invasion assay wells was performed with XTT Reagent kit (XTT, cell proliferation kit, Beit-Ha'Emek, Israel, equivalent to MTT kit) according to manufacturer's protocol.…”

“…In order to detect proteolytic activity of Matrix Metalloproteinases (MMP2, MMP9) in conditioned media (CM) collected after 48e72 h culture, substrate-gel-electrophoresis (Zymography) on gels containing gelatin as the substrate were used as was previously described [27].…”