Molecular Human Reproduction, Vol. 9, No. 6, 367-373,
June 2003
© 2003 European Society of Human Reproduction and Embryology
Article |
Differential activity of the gelatinases (matrix metalloproteinases 2 and 9) in the fetal membranes and decidua, associated with labour
Submitted on January 20, 2003; accepted on February 17, 2003
1 Laboratory for Research in Reproductive Sciences, Department of Obstetrics and Gynecology, Ha’Emek Medical Center, 18101, Afula and 2 Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
3 To whom correspondence should be addressed at: Department of Obstetrics and Gynecology, Ha’Emek Medical Center, Afula 18101, Israel. e-mail: shaleve{at}tx.technion.ac.il
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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 hierarchal activity of the MMPs in the onset of labour allowing rupture of the membranes while avoiding premature placental separation.
Key words: contractions/decidua/fetal membrane/matrix metalloproteinase-2, -9/TIMP
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A number of tightly regulated proteolytic enzyme systems, including the plasminogen activation cascade and matrix metalloproteinases (MMPs), play integral roles in the remodelling of extracellular matrices during pregnancy and parturition. Degradation of the extracellular matrix in fetal membranes has been implicated in the process of parturition, fetal membrane rupture and placental detachment from the decidua and maternal uterus (Tsatas et al., 1999; Maymon et al., 2000; Xu et al., 2002). MMPs are enzymes capable of degrading extracellular matrix including collagen. Tissue inhibitors of matrix metalloproteinases (TIMPs) inhibit the activity of MMPs by covalently binding to the enzymes (Hulboy et al., 1997).
Two gelatinases, gelatinases A and B (also known as MMP-2 and -9 respectively), have been implicated in the mechanisms of membrane rupture (Vadillo-Ortega et al., 1995a,b; Vadillo-Ortega et al., 1998; Ulug et al., 2001; Fortunato and Menon, 2001). However, the exact changes in protease expression and activity during the commencement of labour are not clear. Novel methods now enable determination of the actual enzymatic activity of gelatinases in biological fluids (Mancini et al., 1999; Romanelli et al., 1999; Ratnikov et al., 2000; Gusman et al., 2001).
In this study, we assessed labour-associated changes in gelatinase activity in cultured human amnion, chorion and decidua, as well as in amniotic fluid.
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Patients
Chorion, amnion and decidua were collected from 12 women delivered by scheduled, repeat elective Caesarean section before any regular uterine contractions were recorded (the control group); and from 12 women delivered by Caesarean section while having regular contractions for more than an hour. Ethical approval was granted for the study and all patients gave informed consent. All patients had uncomplicated, singleton, term (38–39 week) pregnancies and were operated on while membranes were intact, described in detail elsewhere (Ulug et al., 2001). Fetal heart rate monitoring was normal in all cases; neither the clinical condition nor sampled specimens gave evidence for infection and in all newborns the 5 min Apgar score was above 7.
Collection of samples
All specimens were collected in aseptic conditions in the operating theatre. All specimens were prepared in our laboratory as described in detail elsewhere (Ulug et al., 2001). Briefly, once the newborn was delivered during the Caesarean section, the placenta was manually removed and placed in a sterile sheet. Superficial amniotic membrane was gently separated from an area above the chorionic plate. Then, the chorionic tissue sample was taken from the denuded area underneath, where the chorion turns from placenta to a membrane. This enabled sampling of chorionic tissue without decidual contamination. A sample was taken from the decidua vera (away from the placental implantation site) by scissors, after removal of the placenta. Following the collection of tissue samples, they were immediately immersed in pre-warmed medium without serum (HTF; Irvine Scientific, CA, USA). The remaining tissue handling was performed under a laminar flow hood. All specimens were washed with HTF to remove any remaining blood before the beginning of the incubation period. No significant difference was found between the viability (as tested by trypan blue exclusion) after overnight incubation versus 72 h of incubation between samples (93 ± 4.6% and 91 ± 5.5%, mean ± SE respectively).
Preparation of samples
Samples of similar size (
0.5 cmx0.5 cm) samples were dissected from each tissue type. Each tissue sample was incubated in 0.5 ml of HTF in 1.7 ml conical tubes with perforated cap, to allow free exchange of gases. The incubation period was 72 h in a 37°C humidified incubator with 95% air and 5% CO2. After the incubation period, the culture media were collected and final fluid volumes measured. The final wet weight of the corresponding tissue block was also determined. All media were stored at –20°C until assay. Assays were performed using media conditioned by 1.0 mg of tissue, except for experiments in which a robust production of MMPs was expected [in which case a reduced amount of tissue (0.5 mg) was used]. This was usually 10–30 µl of conditioned medium.
Substrate-gel-electrophoresis (zymography)
In order to detect proteolytic activity in conditioned media (CM), substrate-gel-electrophoresis (zymography) on gels containing gelatin as the substrate were used. CM, molecular mass markers (10 µl), and standard commercial gelatinases A and B (7 µl; Oncogene Science, Cambridge, MA, USA) were diluted with 4x sample buffer (5% SDS, 20% glycerol in 0.4 mol/l Tris, pH 6.8 containing 0.02% bromophenol blue without 2-mercaptoethanol). Samples were electrophoresed through a 10% polyacrylamide gel containing 1 mg/ml gelatin. After electrophoresis, gelatin gels were washed twice in 2.5% Triton X-100 for 15 min. Gelatin gels were incubated for 24 h at 37°C in 0.2 mol/l NaCl, 5 mmol/l CaCl2, 0.02% Brij 35 and 50 mmol/l Tris, pH 7.5. The buffer was decanted and the gel stained with Coomassie Blue G in 30% methanol and 10% acetic acid for 10 min at room temperature on a rotary shaker. Stain was washed out with water until clear bands were seen. Finally, the gel was incubated for 30 min in 45% methanol, 5% glycerol prior to drying overnight between stretched sheets of cellophane. Areas where proteolytic activity degraded the gelatin are seen as absence of staining. Identification of each gelatinase band was in accordance with its molecular weight and commercial standards (data not shown). These were quantified using the BioImmaging gel documentation system (Dinco & Renium, Jerusalem, Israel) endowed with TINA software (Raytest, Staubenhardt, Germany). In addition, a validation/inhibition study with 10 mmol/l EDTA was performed (data not shown). This procedure chelates the Zn2+ at the active site of MMPs and inhibits their activity (Rao et al., 1995).
Western blot analysis
In order to detect TIMP-1, CM and molecular mass marker (10 µl) were diluted with 4x sample buffer (5% SDS, 20% glycerol in 0.4 mol/l Tris, pH 6.8 containing 0.02% bromophenol blue without 2-mercaptoethanol) and subjected to 10% polyacrylamide gel electrophoresis. After electrophoresis, the CM was adjusted to 1 mg tissue/lane and transferred from the SDS–PAGE onto 0.45 µm nitrocellulose membranes (Scheicher & Schuel, Dassel, Germany). Non-specific binding sites were blocked by incubating the nitrocellulose membranes overnight with 20% non-fat milk and Tris-buffered saline, containing 0.01% Tween-20. The membranes were then washed twice with Tris-buffered saline, containing 0.5% Tween-20, and incubated for 1 h with mouse antihuman TIMP-1 antibody (1.0 µg/ml; Oncogene Science, Cambridge, MA, USA) in 10% non-fat milk and Tris-buffered saline, containing 0.01% Tween-20. The membranes were subsequently washed with Tris-buffered saline, containing 0.5% Tween-20 and incubated for 1 h with horseradish peroxidase-conjugated anti-mouse rabbit secondary antibody (Jackson ImmunoResearch, West Grove, PA, USA) in 10% non-fat milk and Tris-buffered saline, containing 0.01% Tween-20, then detected by enhanced chemiluminescence’s (ECL; Amersham International) and quantified by densitometry as above.
Preparation of soluble biotinylated gelatin
Biotinylated gelatin (BG) was prepared in our laboratory with some modifications of the process described in detail elsewhere. (Rao et al., 1995; Romanelli et al, 1999; Ratnikov et al., 2000; Gusman et al., 2001). Briefly, gelatin (10 mg/ml) was dissolved in 60°C double distilled H2O and left to cool at room temperature. Immuno-pure N-hydroxysuccinimide-LC-biotin (20 mg/ml) was dissolved in dimethylsulphoxide (DMSO). One millilitre of gelatin (10 mg/ml) was incubated with 0.5 ml of biotin (10 mg/ml) for 2 h at room temperature. The reaction was terminated by the addition of 50 µl of 1 mol/l HCl. This preparation was then dialysed within a dialysis sack (cat. no. 250-7u; Sigma, USA) immersed in Tris-buffered saline (TBS: 50 mmol/l Tris pH 7.4, 150 mmol/l NaCl), changed twice per day, for 2 days. The protein concentration of the final solution was measured with a Bio-Rad protein assay kit (Bio-Rad, Munchen, Germany). Subsequently, the BG was divided into aliquots and stored at –70°C until use.
BG was diluted after thawing to 104.1 ng per tube in gelatinase assay buffer (0.05 mol/l Tris pH 7.6, 0.2 mol/l NaCl, 5 mmol/l CaCl2, 0.5 µl of Brij 35 per ml).
Measurement of gelatinase activity by soluble biotinylated gelatin substrate
CM (1–10 µl) in gelatinase assay buffer (0.05 mol/l Tris pH 7.6, 0.2 mol/l NaCl, 5 mmol/l CaCl2, 0.5 µl of Brij 35 per ml) was incubated with 104.1 ng of soluble BG substrate for 18 h at room temperature. Heating the mixture at 100°C for 5 min terminated digestion. Gelatin fragments were separated on 10% polyacrylamide SDS–PAGE gels and transferred to a nitrocellulose membrane. After blocking of non-specific binding sites with blocking buffer (20% non-fat milk and TBS, containing 0.01% Tween-20), the membranes were rinsed with TBS/Tween (0.02 mol/l Tris pH 7.6, 0.14 mol/l NaCl containing 0.1% Tween-20) and incubated with immuno-pure streptavidin and conjugated to horseradish peroxidase, diluted 1/1500 in TBS/tween 0.1%. After a second wash, enhanced chemiluminescence (ECL) reagents were used for detection of BG fragments. The autoradiogram was scanned and the lowest MW band was quantified by computer analysis.
To calculate gelatin cleavage, active MMP-2 was added as positive control (active MMP-2 cleaved 104.1 ng of gelatin in 18 h at room temperature), each autoradiogram was normalized according to its positive control.
Inhibition study
For certain experiments, specific MMP inhibitors were added into the gelatinase assay buffer: MMP-2 Inhibitor I (cat. no. 444244; Calbiochem, USA) or anti MMP-9 antibody (Ab-1, cat. no. IM09L), which is specifically noted as a MMP-9 inhibitor (Oncogene, USA).
MMP gelatinase activity assay kit
BG was incubated with CM for 30 min at 37°C. The cleaved BG was added into 96 well plate coated with streptavidin (which binds biotin). Streptavidin HRP-complex enzyme was added to the bound BG. Coloured substrate was added for 10 min before addition of stop solution. Optical density was measured at 450 nm (cat. no. ECM700; Chemicon, California, USA).
Statistical methods
All data are presented as mean ± SEM. Statistical analysis of the data was carried out by the Student’s t-test when comparing two groups. P < 0.05 was considered significant.
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Establishment of uterine contractions at term increased MMP-2 activity and decreased TIMP-1 protein levels in media conditioned by decidua
Samples of decidua from 12 patients at term with contractions, and 12 patients at term without contractions, were incubated for 72 h in HTF medium. Figure 1A summarizes these 12 cases with a representative zymography gel. On zymography of the CM from the decidua with contractions, both 92 kDa ProMMP-9 and 72 kDa ProMMP-2 were increased 2.1- and 2.6-fold respectively (P < 0.05) versus CM from the decidua without contractions. Formation of a 130 kDa gelatinase band was increased to 2.4-fold (P < 0.05) after contractions began (Figure 1A). A 62 kDa MMP-2, which represents the active form of the enzyme, was detected only in samples taken after contractions began (Figure 1A). Gelatinase activity, as detected by substrate cleavage assay kit (Table I), was significantly higher in the media conditioned by decidua with contractions compared with the decidua without contractions [46.3 ± 9.3 versus 15 ± 5.9 ng gelatinase activity (P < 0.01) respectively]. Similar results were obtained by soluble substrate cleavage assay. Figure 2A (lanes 3–6) reveals an increased activity of gelatinases in the media conditioned by the decidua with contractions compared to decidua without contractions: 101.8 ± 26 versus 31.5 ± 21 ng cleaved BG/18 h respectively (P < 0.01). Specific inhibitors for MMP-9 or MMP-2 did not change the level of gelatinase activity in the media conditioned by decidua without contractions (Figure 3A, lanes 3–5). Conversely, MMP-2 inhibitor suppressed gelatin cleavage in media conditioned by decidua with contractions from 62.8 ± 13 to 26.17 ± 8 ng cleaved BG/18 h (P < 0.05) (Figure 3A, lanes 6–8). MMP-9 inhibitor did not affect gelatinase activity (Figure 3A, lanes 6–8). TIMP-1 expression was decreased by 38.1% (P < 0.05) in the media conditioned by decidua obtained from women with contractions compared with decidua obtained from women with no contractions (Figure 4, lanes 3–4).
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Establishment of uterine contraction at term does not change MMP activity and TIMP-1 level in media conditioned by chorion
Samples of chorion membrane from 12 patients at term with contractions and 12 patients at term without contractions were incubated for 72 h in HTF medium. On zymography of the CM, both 92 kDa ProMMP-9 and 72 kDa ProMMP-2 were increased, 1.8- and 2.4-fold respectively (P < 0.05) with contractions, versus CM from the chorion without contractions (Figure 1C). Gelatinase activity as determined by substrate cleavage assay kit (Table I) was similar in the chorion with contractions compared with the chorion without contractions (26 ± 9.1 versus 18 ± 11.4 ng gelatinase activity respectively).
Similar results were obtained by soluble substrate cleavage assay. Figure 2A (lanes 7–10) reveals a similar activity of gelatinases in the chorion with contractions compared with chorion without contractions: 64.3 ± 38 versus 57.1 ± 40 ng cleaved BG/18 h respectively (P = 0.307). MMP-2 inhibitor reduced BG cleavage by 60% in chorion without contractions (Figure 3B, lanes 3–5) and with contractions (lanes 6–8) from 78.5 ± 26 and 83.1 ± 28 ng cleaved BG/18 h to 31.4 ± 10 and 30 ± 8 ng cleaved BG/18 h respectively (P < 0.05). MMP-9 inhibitor did not affect gelatinase activity (Figure 3B). Expression of TIMP-1 was similar in the chorion with or without contractions (Figure 4, lanes 5–6).
Establishment of uterine contractions at term increased MMP-9 activity and decreased TIMP-1 protein levels in media conditioned by amnion
Samples of amnion from 12 patients at term with contractions and 12 patients at term without contractions were incubated for 72 h in HTF medium. On zymography of the CM from amnion, both 92 kDa ProMMP-9 and 72 kDa ProMMP-2 were increased 3.5- and 2.1-fold respectively (P < 0.05) in amnion obtained from women having contractions compared with amnion from women not having contractions (Figure 1B). Formation of a 130 kDa gelatinase band was increased 2.7-fold (P < 0.05) after contractions began (Figure 1B). Gelatinase activity as determined by substrate cleavage assay kit (Table I) was significantly higher in the amnion with contractions compared to the amnion without contractions [72 ± 14.9 versus 18.7 ± 7.1 ng gelatinase activity (P < 0.01) respectively]. Similar results were obtained by soluble substrate cleavage assay. Figure 2B shows an increased activity of gelatinases in the amnion with contractions (lanes 5–6) compared to amnion without contractions (lanes 3–4): 96.6 ± 27 versus 24.15 ± 23 ng cleaved BG/18 h respectively (P < 0.01). MMP-9 inhibitor significantly decreased gelatin cleavage in the amnion with or without contractions (Figure 3, lanes 3–8), by 92 and 65% respectively [59.67 ± 12 to 3.1 ± 3 ng cleaved BG/18 h and 20.94 ± 6 to 5.23 ± 2 ng cleaved BG/18 h (P < 0.05)]. MMP-2 inhibitor did not affect gelatinase activity (Figure 3). TIMP-1 was significantly decreased to 70% of control level (P < 0.05) in the amnion after contractions (Figure 4, lanes 1–2).
Establishment of uterine contractions at term increases amniotic fluid levels of MMP-9 over MMP-2 and decreases TIMP-1 levels
The dominant MMP expressed in term amniotic fluid obtained from women not having contractions at Caesarean section was 72 kDa ProMMP-2 (Figure 5A); TIMP-1 was also detected in the amniotic fluid (Figure 6A). The dominant MMP expressed in amniotic fluid from women having contractions was 92 kDa ProMMP-9 (Figure 5B), whereas TIMP-1 was reduced (Figure 6B).
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Several MMPs were elevated in the feto–maternal interface following the establishment of contractions. In all three compartments (amnion, chorion and decidua) 92 kDa ProMMP-9 and 72 kDa ProMMP-2 were significantly elevated after contractions began. However, the change of MMP-2 activity in the decidua and the change of MMP-9 activity in the amnion appear to differ. The decidua and fetal membranes use different MMP enzymes to hydrolyse collagen for placental detachment and fetal membrane rupture. A 130 kDa gelatinase band was also elevated in the decidua and amnion after contractions began. We can assume that this 130 kDa gelatinase band is most probably a hetero-dimer of MMP-9. It is known that MMP-9 is secreted from cells as a monomer or a dimer form. MMP-9 is able to create homo-dimers, which are observed on gel zymography as a 210 kDa gelatinase band (Olson et al., 2000). It is documented that a 130 kDa hetero-dimer of MMP-9 exists but the complex is not necessarily a MMP-9-TIMP-1 dimer. In neutrophils, a 125–130 kDa form of MMP-9 was found to be a hetero-dimer of MMP-9-Lipocalin complex (Olson et al., 2000). In breast carcinoma, a 125–130 kDa form of MMP-9 was observed after immunoprecipitation (Olson et al., 2000).
TIMP-1 serves as a physiological inhibitor for all MMP enzymes, in particular MMP-9, which is considered to be a key MMP in membrane rupture. We have studied the secretion of TIMP-1 in each compartment and found that MMP elevation was followed by significant reduction in TIMP-1 expression in the decidua and amnion but not in the chorion, resulting in an increased MMP/TIMP-1 ratio in the first two compartments.
The MMP content of amniotic fluid changes after contractions from predominantly MMP-2 and TIMP-1 expression to high MMP-9 and lower MMP-2 and TIMP-1 levels. This appears to agree with the results of previous studies. In the chorioamnion membrane and amniotic fluid, the MMP/TIMP ratio increased after contractions began (Lei et al., 1995; Vadillo-Ortega et al., 1995ab; Vadillo-Ortega et al., 1998; Tsatas et al., 1999; Maymon et al., 2000; 2001; Xu et al., 2002). In these studies reduction in TIMP-1 and TIMP-2 levels was found in amniotic fluid after contractions. Maymon et al. (2000) found that the active form of MMP-9 was detectable in amniotic fluid after the appearance of contractions or membrane rupture regardless of gestational age. We found the active form of MMP-9 in media conditioned by amnion as well as in amniotic fluid after contractions began. We also found production of the active form of MMP-2 in the media conditioned by the decidua and chorion after contractions.
Zymography measures all forms of MMP (active and inactive), it therefore does not reliably represent the true physiological activity, which is influenced by the presence of MMP inhibitors and activators. MMP activator–inhibitor complexes are disassembled on gel zymography, and as a result of this separation, all forms of MMP are shown on zymography. In vivo, only the active forms of MMP, which are not bound with natural inhibitors such as TIMP, can cleave the substrate. The search for a more accurate estimation of the true physiological enzyme activity led us to measure the cleavage of biotinylated substrates (Mancini et al., 1999; Romanelli et al., 1999; Ratnikov et al., 2000; Gusman et al., 2001). By using BG as a soluble substrate, we can add labelled gelatin into CM where MMPs are in their natural form and complexes, i.e. monomers and dimers, pro and active form, bound or free from specific inhibitors. Since gelatin is mostly gelatinase substrate, one may assume that its cleavage will be a net result of MMP-9 and MMP-2 activity. In contrast to the high levels of expression of MMP-9 and MMP-2 demonstrated on zymography from the three compartments without contractions, the endogenous gelatinolytic activity was minimal. With contractions, the physiological gelatinolytic activity is significantly increased in the decidua and amnion but not in the chorion. Using specific inhibitors for MMP-2 and MMP-9 we have shown that in each of the compartments, the gelatinolytic activity measured by BG substrate cleavage assay could be attributed to a different MMP enzyme. In the amnion, most of the gelatinolytic activity is contributed by MMP-9, this is in agreement with other studies showing expression shift towards MMP-9 in the amnion and amniotic fluid after contractions (Lei et al., 1995; Vadillo-Ortega et al., 1995a;b; Tstas et al., 1999; Maymon et al., 2000). In the decidua, most of the gelatinolytic activity is contributed by MMP-2. Maj and Kankofer (1997) reported expression of active MMP-2 in decidua obtained from cows. Moreover, in cases of placental retention in these cows, the amount of the active form of MMP-2 was significantly reduced, suggesting that MMP-2 might be critical for placental separation.
Qin et al. (1997a;b) found that a week before contractions appear, the decidua secretes two types of relaxin, H1 and H2, which increase ProMMP-9 secretion in the fetal membranes, but have no influence on TIMP or MMP-2. In their study, they suggested that relaxin might serve as a paracrine/autocrine factor of the decidua to induce amnion rupture.
The labour regulatory process might involve cross talk between the maternal and fetal compartments. Recently Xu et al. (2002) found differential cell-specific expression of MMP in human placenta, indicating possible different MMP activity at different sites. We cannot exclude the possibility that the decidua regulates rupture of the amnion via an increase in MMP-9 expression and activation. This, together with the possibility of separate regulation of decidua disintegration by MMP-2 and probably other factors, could provide a mechanism for activity of MMP in the onset of labour avoiding premature placental separation.
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REFERENCES |
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Fortunato, S.J. and Menon, R. (2001) Distinct molecular events suggest different pathways for preterm labor and premature rupture of membranes. Am. J. Obstet. Gynecol., 184, 1399–1405.[CrossRef][ISI][Medline]
Gusman, H., Travis, J., Helmerhorst, E.J., Potempa, J., Troxler, R.F. and Oppenheim, F.G. (2001) Salivary histatin 5 is an inhibitor of both host and bacterial enzymes implicated in periodontal disease. Infect. Immun., 69, 1402–1408.
Hulboy, D.L., Rudolph, L.A. and Matrisian, L.M. (1997) Matrix metalloproteinases as mediators of reproductive function. Mol. Hum. Reprod., 3, 27–45.
Lei, H., Vadillo-Ortega, F., Paavola, L.G., Strauss, J.F, 3rd (1995) 92-kDa gelatinase (matrix metalloproteinase-9) is induced in rat amnion immediately prior to parturition. Biol. Reprod., 53, 339–344.[Abstract]
Maj, J.G., and Kankofer, M. (1997) Activity of 72-kDa and 92-kDa matrix metalloproteinases in placental tissues of cows with and without retained fetal membranes. Placenta, 18, 683–687.[CrossRef][Medline]
Mancini, S., Romanelli, R., Laschinger, C.A., Overall, C.M., Sodek, J. and McCulloch, C.A. (1999) Assessment of a novel screening test for neutrophil collagenase activity in the diagnosis of periodontal diseases. J. Periodontol., 70, 1292–1302.[CrossRef][Medline]
Maymon, E., Romero, R., Pacora, P., Gervasi, M.T., Gomez, R., Edwin, S.S. and Yoon, B.H. (2000) Evidence of in vivo differential bioavailability of the active forms of matrix metalloproteinases 9 and 2 in parturition, spontaneous rupture of membranes, and intra-amniotic infection. Am. J. Obstet. Gynecol., 183, 887–894.[CrossRef][ISI][Medline]
Maymon, E., Romero, R., Pacora, P., Gomez, R., Mazor, M., Edwin, S., Chaiworapongsa, T., Kim, J.C., Yoon, B.H., Menon, R. et al. (2001) A role for the 72 kDa gelatinase (MMP-2) and its inhibitor (TIMP-2) in human parturition, premature rupture of membranes and intraamniotic infection. J. Perinat. Med., 29, 308–316.[CrossRef][ISI][Medline]
Olson, M.W., Bernardo, M.M., Pietila, M., Gervasi, D.C., Toth, M., Kotra, L.P., Massova, I.,Mobashery, S. and Fridman, R. (2000) Characterization of the monomeric and dimeric forms of latent and active Matrix Metalloproteinase-9. J. Biol. Chem., 275, 2661–2668.
Qin, X., Chua, P.K., Ohira, R.H. and Bryant-Greenwood, G.D. (1997a) An autocrine/paracrine role of human decidual relaxin. II. Stromelysin-1 (MMP-3) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1). Biol. Reprod., 56, 812–817.[Abstract]
Qin, X., Garibay-Tupas, J., Chua, P.K., Cachola, L. and Bryant-Greenwood, G.D. (1997b) An autocrine/paracrine role of human decidual relaxin. I. Interstitial collagenase (matrix metalloproteinase-1) and tissue plasminogen activator. Biol. Reprod., 56, 800–812.[Abstract]
Rao, V.H., Bridge, J.A., Neff, J.R., Schaefer, G.B., Buehler, B.A, Vishwanatha, J.K., Pollock, R.E., Nicolson, G.L, Yamamoto, M., Gokaslam, Z.L. et al. (1995) Expression of 72 kDa and 92kDa type IV collagenases from human giant cell tumor of bone. Clin. Exp. Metastasis, 13, 420–426.[CrossRef][ISI][Medline]
Ratnikov, B., Deryugina, E., Leng, J., Marchenko, G., Dembrow, D. and Strongin, A. (2000) Determination of matrix metalloproteinase activity using biotinylated gelatin. Anal. Biochem., 286, 149–155.[CrossRef][Medline]
Romanelli, R., Mancini, S., Laschinger, C., Overall, C.M., Sodek, J. and McCulloch, C.A. (1999) Activation of neutrophil collagenase in periodontitis. Infect. Immun., 67, 2319–2326.
Tsatas, D., Baker, M.S. and Rice, G.E. (1999) Differential expression of proteases in human gestational tissues before, during and after spontaneous-onset labour at term. J. Reprod. Fertil., 116, 43–49.[Abstract]
Ulug, U., Goldman, S., Ben-Shlomo, I. and Shalev, E. (2001) Matrix metalloproteinase (MMP)-2 and MMP-9 and their inhibitor, TIMP-1, in human term decidua and fetal membranes: the effect of prostaglandin F(2alpha) and indomethacin. Mol. Hum. Reprod., 7, 1187–1193.
Vadillo-Ortega, F., Gonzalez-Avila, G., Furth, E.E., Lei, H., Muschel, R.J., Stetler-Stevenson, W.G. and Strauss, J.F, 3rd (1995a) 92-kd type IV collagenase (matrix metalloproteinase-9) activity in human amniochorion increases with labor. Am. J. Pathol., 146, 148–156.[Abstract]
Vadillo-Ortega, F., Hernandez Miranda, A., Bermejo Martinez, L., Beltran Montoya, J. and Gonzalez Avila, G. (1995b) Transition from the latent to the active enzymatic form as a model of regulation of extracellular matrix degradation in the chorioamnion during human labor. Ginecol. Obstet. Mex., 63, 166–172.[Medline]
Vadillo-Ortega, F., Arechevaleta, F. and Beltran Montoya, J. (1998) Apoptosis and extracellular matrix degradation in chorio-amnion during labor and premature membrane rupture. Ginecol. Obstet. Mex., 66, 202–207.[Medline]
Xu, P., Alfaidy, N. and Challis, J.R. (2002) Expression of matrix metalloproteinase (MMP)-2 and MMP-9 in human placenta and fetal membranes in relation to preterm and term labor. J. Clin. Endocrinol. Metab., 87, 1353–1361.
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 T. M Lindstrom and P. R Bennett The role of nuclear factor kappa B in human labour Reproduction, November 1, 2005; 130(5): 569 - 581. [Abstract] [Full Text] [PDF]
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S. Mahameed, S. Goldman, D. Gabarin, A. Weiss, and E. Shalev The Effect of Serum From Women With Preeclampsia on JAR (trophoblast-like) Cell Line Reproductive Sciences, September 1, 2005; 12(6): e45 - e50. [Abstract] [PDF]
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 S. Goldman, A. Weiss, I. Almalah, and E. Shalev Progesterone receptor expression in human decidua and fetal membranes before and after contractions: possible mechanism for functional progesterone withdrawal Mol. Hum. Reprod., April 1, 2005; 11(4): 269 - 277. [Abstract] [Full Text] [PDF]
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 W. Li, N. Alfaidy, and J. R. G. Challis Expression of Extracellular Matrix Metalloproteinase Inducer in Human Placenta and Fetal Membranes at Term Labor J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2897 - 2904. [Abstract] [Full Text] [PDF]
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