A role for matrix metalloproteinase-9 in spontaneous rupture of the fetal membranes

N. Athayde, S. S. Edwin, R. Romero, R. Gomez, E. Maymon, P. Pacora, Ramkumar Menon

Research output: Contribution to journalArticle

166 Citations (Scopus)

Abstract

OBJECTIVES: 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. STUDY DESIGN: 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. RESULTS: 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). CONCLUSION: Our data support a role for matrix metalloproteinase-9 in the mechanisms responsible for membrane rupture in term and preterm gestations.

Original languageEnglish (US)
Pages (from-to)1248-1253
Number of pages6
JournalAmerican Journal of Obstetrics and Gynecology
Volume179
Issue number5
StatePublished - 1998
Externally publishedYes

Fingerprint

Extraembryonic Membranes
Spontaneous Rupture
Matrix Metalloproteinase 9
Membranes
Rupture
Amniotic Fluid
Tissue Inhibitor of Metalloproteinase-1
Premature Obstetric Labor
Matrix Metalloproteinase Inhibitors
Collagen
Premature Rupture Fetal Membranes
Chorion
Pregnancy
Amnion
Amniocentesis
Matrix Metalloproteinases
Immunoassay
Gestational Age
Extracellular Matrix

Keywords

  • Amniotic fluid
  • Chorioamnionitis
  • Gelatinase B
  • Matrix metalloproteinases
  • Microbial invasion of amniotic cavity
  • Premature rupture of the membranes
  • Prematurity

ASJC Scopus subject areas

  • Medicine(all)
  • Obstetrics and Gynecology

Cite this

Athayde, N., Edwin, S. S., Romero, R., Gomez, R., Maymon, E., Pacora, P., & Menon, R. (1998). A role for matrix metalloproteinase-9 in spontaneous rupture of the fetal membranes. American Journal of Obstetrics and Gynecology, 179(5), 1248-1253.

A role for matrix metalloproteinase-9 in spontaneous rupture of the fetal membranes. / Athayde, N.; Edwin, S. S.; Romero, R.; Gomez, R.; Maymon, E.; Pacora, P.; Menon, Ramkumar.

In: American Journal of Obstetrics and Gynecology, Vol. 179, No. 5, 1998, p. 1248-1253.

Research output: Contribution to journalArticle

Athayde, N, Edwin, SS, Romero, R, Gomez, R, Maymon, E, Pacora, P & Menon, R 1998, 'A role for matrix metalloproteinase-9 in spontaneous rupture of the fetal membranes', American Journal of Obstetrics and Gynecology, vol. 179, no. 5, pp. 1248-1253.
Athayde N, Edwin SS, Romero R, Gomez R, Maymon E, Pacora P et al. A role for matrix metalloproteinase-9 in spontaneous rupture of the fetal membranes. American Journal of Obstetrics and Gynecology. 1998;179(5):1248-1253.
Athayde, N. ; Edwin, S. S. ; Romero, R. ; Gomez, R. ; Maymon, E. ; Pacora, P. ; Menon, Ramkumar. / A role for matrix metalloproteinase-9 in spontaneous rupture of the fetal membranes. In: American Journal of Obstetrics and Gynecology. 1998 ; Vol. 179, No. 5. pp. 1248-1253.
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T1 - A role for matrix metalloproteinase-9 in spontaneous rupture of the fetal membranes

AU - Athayde, N.

AU - Edwin, S. S.

AU - Romero, R.

AU - Gomez, R.

AU - Maymon, E.

AU - Pacora, P.

AU - Menon, Ramkumar

PY - 1998

Y1 - 1998

N2 - OBJECTIVES: 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. STUDY DESIGN: 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. RESULTS: 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). CONCLUSION: Our data support a role for matrix metalloproteinase-9 in the mechanisms responsible for membrane rupture in term and preterm gestations.

AB - OBJECTIVES: 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. STUDY DESIGN: 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. RESULTS: 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). CONCLUSION: Our data support a role for matrix metalloproteinase-9 in the mechanisms responsible for membrane rupture in term and preterm gestations.

KW - Amniotic fluid

KW - Chorioamnionitis

KW - Gelatinase B

KW - Matrix metalloproteinases

KW - Microbial invasion of amniotic cavity

KW - Premature rupture of the membranes

KW - Prematurity

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