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      Prolidase, Matrix Metalloproteinases 1 and 13 Activity, Oxidative-Antioxidative Status as a Marker of Preterm Premature Rupture of Membranes and Chorioamnionitis in Maternal Vaginal Washing Fluids

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          Abstract

          Objective: Etiology of premature preterm rupture of membranes (PPROM) is not yet completely known and chorioamnionitis is one of the most important complications of its. We aimed to evaluate whether prolidase, matrix metalloproteinases, oxidative-antioxidative status, and inflammation markers in vaginal washing fluid (VWF) were associated with etiology of PPROM and whether these markers could be used to predict chorioamnionitis in PPROM.

          Study Design: This prospective case control study enrolled fifty pregnant women with PPROM and 50 healthy pregnant women. The VWF samples were taken at the time of admission in the PPROM group and patients were followed for chorioamnionitis. Prolidase, matrix metalloproteinases, oxidative-antioxidative status, and inflammation markers in VWF were assayed.

          Results: VWF levels of prolidase, matrix metalloproteinases 1-13 (p< 0.001), oxidative stress parameters, total oxidative stress (TOS) (p < 0.001) and oxidative stress index (OSI) (p = 0.002), and hs-CRP (p = 0.045) were significantly higher in the PPROM group than in the controls. Antioxidative status parameters, levels of paroxanase (PON-1) (p < 0.001) and total antioxidant capacity (TAC) (p < 0.001), were significantly lower in the PPROM group than in the controls. Mean VWF levels of prolidase (p < 0.001), metalloproteinases (p<0.05), and oxidative-antioxidative status parameters (p<0.05) were significantly different in women with versus women without chorioamnionitis in the PPROM group. Prolidase, MMP-13, TOS, TAC, and PON-1 were found as important predictors for chorioamnionitis in the PPROM group by the multivariate logistic regression analysis. When the ROC curve analysis for prolidase, MMP-13, TOS, TAC, and PON-1 were performed, all of them were statistically significant for area under the curve (areas under the curve were 0.94, 0.90, 0.80, 0.25, and 0.19, respectively).

          Conclusions: This study showed that collagen turnover mediators, especially prolidase, and increased oxidative stress are significantly associated with PPROM. Also, chorioamnionitis can be predicted with prolidase, MMP-13, TOS, TAC, and PON-1 in PPROM patients.

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          Most cited references34

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          Preterm premature rupture of the membranes.

          M Mercer (2002)
          Preterm premature rupture of membranes (PROM) affects over 120,000 pregnancies annually in the United States and is associated with significant maternal, fetal, and neonatal risk. Management of PROM requires an accurate diagnosis as well as evaluation of the risks and benefits of continued pregnancy or expeditious delivery. An understanding of gestational age-dependent neonatal morbidity and mortality is important in determining the potential benefits of conservative management of preterm PROM at any gestation. Where possible, the treatment of pregnancies complicated by PROM remote from term should be directed towards conserving the pregnancy and reducing perinatal morbidity due to prematurity while monitoring closely for evidence of infection, placental abruption, labor, or fetal compromise due to umbilical cord compression. Current evidence suggests aggressive adjunctive antibiotic therapy to reduce gestational age-dependent and infectious infant morbidity. Similarly, review of evaluable data indicates that antenatal corticosteroid administration in this setting enhances neonatal outcome without increasing the risk of perinatal infection. It is not clear that tocolysis in the setting of preterm PROM remote from term reduces infant morbidity. When preterm PROM occurs near term, particularly if fetal pulmonary maturity is evident, the patient is generally best served by expeditious delivery.
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            The human serum paraoxonase/arylesterase polymorphism.

            B Du, H W Eckerson, C Wyte (1983)
            The heterozygous human serum paraoxonase phenotype can be clearly distinguished from both homozygous phenotypes on the basis of its distinctive ratio of paraoxonase to arylesterase activities. A trimodal distribution of the ratio values was found with 348 individual serum samples, measuring the ratio of paraoxonase activity (with 1 M NaCl in the assay) to arylesterase activity, using phenylacetate. The three modes corresponded to the three paraoxonase phenotypes, A, AB, and B (individual genotypes), and the expected Mendelian segregation of the trait was observed within families. The paraoxonase/arylesterase activity ratio showed codominant inheritance. We have defined the genetic locus determining the aromatic esterase (arylesterase) responsible for the polymorphic paraoxonase activity as esterase-A (ESA) and have designated the two common alleles at this locus by the symbols ESA*A and ESA*B. The frequency of the ESA*A allele was estimated to be .685, and that of the ESA*B allele, 0.315, in a sample population of unrelated Caucasians from the United States. We postulate that a single serum enzyme, with both paraoxonase and arylesterase activity, exists in two different isozymic forms with qualitatively different properties, and that paraoxon is a "discriminating" substrate (having a polymorphic distribution of activity) and phenylacetate is a "nondiscriminating" substrate for the two isozymes. Biochemical evidence for this interpretation includes the cosegregation of the degree of stimulation of paraoxonase activity by salt and paraoxonase/arylesterase activity ratio characteristics; the very high correlation between both the basal (non-salt stimulated) and salt-stimulated paraoxonase activities with arylesterase activity; and the finding that phenylacetate is an inhibitor for paraoxonase activities in both A and B types of enzyme.
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              A role for matrix metalloproteinase-9 in spontaneous rupture of the fetal membranes.

              Neil Athayde, Samuel Edwin, Roberto Romero … (1998)
              Preterm premature rupture of fetal membranes is responsible for 30% to 40% of preterm deliveries. Fetal membranes are composed primarily of collagen. Matrix metalloproteinases are enzymes capable of degrading extracellular matrix macromolecules, including collagens. Expression of matrix metalloproteinase-9 (gelatinase B, 92 kd) and its tissue inhibitor (tissue inhibitor of metalloproteinase-1) has been localized in amnion and chorion. The objective of this study was to determine whether rupture of fetal membranes and intrauterine infection are associated with changes in the expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1. Two hundred one women in the following categories had amniotic fluid retrieved: (1) preterm labor and intact membranes in the presence (n = 42) or absence (n = 21) of microbial invasion of the amniotic cavity, (2) preterm premature rupture of the membranes with (n = 29) or without (n = 23) microbial invasion of the amniotic cavity, and (3) term gestation with intact membranes (n = 50) or with premature rupture of the membranes (n = 40). Women in groups 1 and 2 were matched for gestational age at amniocentesis. Microbial invasion of the amniotic cavity was defined by a positive amniotic fluid culture for micro-organisms. Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 were measured with use of sensitive and specific immunoassays that were validated for amniotic fluid. Spontaneous rupture of membranes at term is associated with a significant increase in the amniotic fluid concentrations of matrix metalloproteinase-9 (premature rupture of membranes, no labor: median 3.9 ng/mL, range 2. 7 to 11.1 ng/mL vs no premature rupture of membranes, no labor: median <0.4 ng/mL, range <0.4 to 22.4 ng/mL; P <.001). Patients with preterm premature rupture of the membranes had higher median matrix metalloproteinase-9 concentrations than those with preterm labor and intact membranes who were delivered at term (7.6 ng/mL, range <0.4 to 230.81 ng/mL vs <0.4 ng/mL, range <0.4 to 1650 ng/mL; P =.06). Women with microbial invasion of the amniotic cavity had higher median matrix metalloproteinase-9 concentrations than did those without microbial invasion regardless of membrane status (preterm labor: 54.5 ng/mL, range <0.4 to 3910 ng/mL vs <0.4 ng/mL, range <0. 4 to 1650 ng/mL; P <.01; preterm premature rupture of membranes: 179. 8 ng/mL, range <0.4 to 611 ng/mL vs 7.6 ng/mL, range <0.4 to 230.81; P <.001). Our data support a role for matrix metalloproteinase-9 in the mechanisms responsible for membrane rupture in term and preterm gestations.
              Article 0 comments Cited 38 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Med Sci
                Journal ID (iso-abbrev): Int J Med Sci
                Journal ID (publisher-id): ijms
                Title: International Journal of Medical Sciences
                Publisher: Ivyspring International Publisher (Sydney )
                ISSN (Electronic): 1449-1907
                Publication date Collection: 2013
                Publication date (Electronic): 15 August 2013
                Volume: 10
                Issue: 10
                Pages: 1344-1351
                Affiliations
                1. Department of Gynecology and Obstetrics, Faculty of Medicine, Dicle University, Diyarbakir, Turkey
                2. Department of Biochemistry, Faculty of Medicine, Dicle University, Diyarbakir, Turkey
                3. Department of Bioistatistic, Faculty of Medicine, Dicle University, Diyarbakir, Turkey
                Author notes
                ✉ Corresponding author: Dr. Hatice Ender SOYDINC, 1. Department of Gynecology and Obstetrics, Faculty of Medicine, Dicle University, Diyarbakir, Turkey. Email: endersoydinc@ 123456hotmail.com ; Tel: +90 412 2488001/4904; Fax: +90412 2488523.

                Competing Interests: The authors have declared that no competing interest exists.

                Article
                Publisher ID: ijmsv10p1344
                DOI: 10.7150/ijms.4802
                PMC ID: 3752722
                PubMed ID: 23983595
                SO-VID: fb8035f9-d0d7-4a7b-bbcf-d32147480ed3
                Copyright © © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.
                History
                Date received : 1 July 2012
                Date accepted : 25 January 2013
                Categories
                Subject: Research Paper

                ScienceOpen disciplines: Medicine
                Keywords: premature preterm rupture of membrane,chorioamnionitis,prolidase,matrix metalloproteinases,total oxidative status,total antioxidative capacity,paraoxonase-1,vaginal washing fluid.
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: premature preterm rupture of membrane, chorioamnionitis, prolidase, matrix metalloproteinases, total oxidative status, total antioxidative capacity, paraoxonase-1, vaginal washing fluid.

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