Matrix metalloproteinases-9 in preterm and term human parturition

Athayde, Neil; Romero, Roberto; Gomez, Ricardo; Maymon, Eli; Pacora, Percy; Mazor, Moshe; Yoon, Bo Hyun; Fortunato, Stephen J.; Menon, Ramkumar; Ghezzi, Fabio; Edwin, Samuel S.

doi:10.1002/(sici)1520-6661(199909/10)8:5<213::aid-mfm3>3.0.co;2-r

Cited by 91 publications

(28 citation statements)

References 21 publications

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“…MMP3 cleaves a number of substrates including proteoglycans, fibronectins, gelatins, collagen IV, and V (Hulboy et al 1997). A number of studies have suggested that these enzymes have been implicated in the process of parturition, rupture of membranes, and intra amniotic infection (Athayde et al 1999, Maymon et al 2000a, 2000b, 2000c. However, there is no information on the placental levels of these MMPs in preterm deliveries.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Sundrani¹,

Chavan‐Gautam²,

Pisal³

et al. 2013

Reproduction

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Maternal nutrition is an important determinant of one-carbon metabolism and defects in the one-carbon metabolism may lead to poor obstetric outcomes. This study was designed to test the hypothesis that altered intake/metabolism of micronutrients (folic acid and vitamin B 12 ) and docosahexaenoic acid (DHA) contributes to increased homocysteine and oxidative stress leading to altered levels of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in women delivering preterm. We have earlier reported increased vitamin B 12 , homocysteine, and oxidative stress along with reduced placental DHA in women delivering preterm. In this study, we further examine the placental levels of MMP2, MMP3, TIMP1, and TIMP2 in 75 women delivering at term and 73 women delivering preterm. Placental levels of MMPs and TIMPs were determined by ELISA. Placental MMP2 and MMP3 levels were higher (P!0.01) in women delivering preterm as compared with term. There was no difference in the placental TIMP1 and TIMP2 levels in women delivering preterm and at term. Further placental MMP2 and MMP3 levels were higher (P!0.01) in women with preterm labor as compared with those in labor at term, suggesting that MMPs may favor degradation of extracellular matrix in the placenta during preterm labor. Our study for the first time suggests a crucial role of micronutrients and MMPs in preterm birth. Future studies need to examine if epigenetic modifications through the one-carbon cycle contribute to increased levels of MMPs leading to preterm deliveries.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Sundrani¹,

Chavan‐Gautam²,

Pisal³

et al. 2013

Reproduction

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“…The expression of MMP-1, MMP-2, MMP-3, MMP-9, MMP-10, MMP-11 mRNA was confirmed in amnion and chorion in preterm as well as in term patients. It was also investigated that amniotic fluid concentration of MMP-1, MMP-2 and MMP-3 increase during the labour [16][17][18][19][20][21]. MMP-7 and MMP-8 mRNA were not found in amniochorionic tissue, but MMP-8 was detected in the amniotic fluid.…”

Section: Discussionmentioning

confidence: 99%

“…MMP-7 and MMP-8 mRNA were not found in amniochorionic tissue, but MMP-8 was detected in the amniotic fluid. In amniotic fluid concentration of MMP-8 also raised during the active stage of labour [21][22][23]. There was not found research studies confirming the role of MMP-12 and MMP-13 with pPROM patients.…”

Section: Discussionmentioning

confidence: 99%

Total matrix metalloproteinase-8 serum levels in patients labouring preterm and patients with threatened preterm delivery.

Kuć

Lemancewicz²,

Laudański³

et al. 2010

Folia Histochem Cytobiol.

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Preterm labour and prematurity are still a main cause of perinatal morbidity nowadays. The aim of our study was to assess the role of MMP-8 as a predictive marker of preterm delivery. Four groups of patients were involved to the study: I -pregnant women at 24-34 weeks of gestation with any symptoms of threatened preterm labour; II -threatened preterm labour patients between 24-34 weeks of gestation; III -preterm vaginal delivery patients; IV -healthy term vaginal delivery patients. Serum concentration of total MMP-8 was measured using two enzyme-linked immunosorbent assays. There were no significant differences in the median concentrations of total MMP-8 between physiological pregnancy and threatened preterm labour patients with existing uterine contractility. No significant differences of total MMP-8 were either found between healthy term and preterm labouring patients. The studies on a larger population are needed to reject the hypothesis that preterm labour is connected with increased MMP-8 plasma concentrations of women in preterm labour and threatened preterm delivery.

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“…MMP2 is a constitutive enzyme, while MMP9 is inducible in response to infection. 140 Both have been found in amniotic fluid [141][142][143][144][145] and the activity and concentration of MMP9 is increased in the amniotic fluid of women with preterm labor and intact membranes, as well as in women with preterm PROM. 141;143 We have previously reported that amniotic fluid TIMP2 concentrations are low in women with spontaneous labor (term and preterm), with intact or ruptured membranes, regardless of the microbial status of the amniotic cavity.…”

Section: Single Locus Analysis For Mothersmentioning

confidence: 99%

14: Identification of fetal and maternal single nucleotide polymorphisms in candidate genes that predispose to spontaneous preterm labor with intact membranes

Romero¹,

Velez²,

Mazaki‐Tovi³

et al. 2009

American Journal of Obstetrics and Gynecology

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Objective-To determine whether maternal/fetal SNPs in candidate genes are associated with spontaneous preterm labor/delivery. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptStudy Design-A genetic association study was conducted in 223 mothers and 179 fetuses [preterm labor with intact membranes who delivered <37 weeks (PTB)], and 599 mothers and 628 fetuses (normal pregnancy): 190 candidate genes and 775 SNPs were studied. Single locus/ haplotype association analyses were performed; FDR was used to correct for multiple testing (q*=0.15)]. Results-1)The strongest single locus associations with PTB were IL6R (fetus: p=0.000148) and TIMP2 (mother: p=0.000197), remaining significant after correction for multiple comparisons; 2) Global haplotype analysis indicated an association between a fetal DNA variant in IGF2 and maternal COL4A3 (global p=0.004 and 0.007, respectively).Conclusion-A SNP involved in controlling fetal inflammation (IL6R) and DNA variants in maternal genes encoding for proteins involved in extracellular matrix biology approximately doubled the risk of PTB.

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Matrix metalloproteinases-9 in preterm and term human parturition

Cited by 91 publications

References 21 publications

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

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

Total matrix metalloproteinase-8 serum levels in patients labouring preterm and patients with threatened preterm delivery.

14: Identification of fetal and maternal single nucleotide polymorphisms in candidate genes that predispose to spontaneous preterm labor with intact membranes

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