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Expression of bone morphogenetic protein 2 in normal spontaneous labor at term, preterm labor, and preterm premature
Gi Jin Kim1, Roberto Romero, Helena Kuivaniemi
1Perinatology Research Branch, National Institute of Child Health and Human Development/National Institutes of Health/Department of Health and Human Services, Bethesda, MD, USA.
Objective:
Genome-wide screening studies of the chorioamniotic membranes unexpectedly identified an increase in the expression of bone morphogenetic protein 2 in spontaneous labor at term. The objective of this study was to determine whether bone morphogenetic protein 2 messenger RNA and protein expression are altered in the chorioamniotic membranes of patients with term labor, preterm labor, and preterm premature rupture of membranes.
Study Design:
Chorioamniotic membranes were obtained from patients at term (with and without labor), with preterm labor (with and without histologic chorioamnionitis), and with preterm premature rupture of membranes (with and without histologic chorioamnionitis). The expression of bone morphogenetic protein 2 was studied by real-time quantitative reverse transcriptase-polymerase chain reaction (n = 88) and immunohistochemistry (n = 124). Nonparametric statistics were used for analysis. Primary amnion cells obtained from women at term not in labor were treated with bone morphogenetic protein 2 to examine whether there was increased prostaglandin E2 expression.
Results:
The median bone morphogenetic protein 2 messenger RNA and protein expression were significantly higher in the membranes of patients with spontaneous labor at term than in those of patients not in labor at term (P < .001 for both). Bone morphogenetic protein 2 messenger RNA and protein expression were increased in patients with preterm labor with histologic chorioamnionitis than in those without histologic chorioamnionitis (P < .05 and P < .001, respectively). There was no difference in bone morphogenetic protein 2 messenger RNA and protein expression in patients with preterm premature rupture of membranes, regardless of chorioamnionitis (P = .13 and P = .08, respectively). There was a correlation between bone morphogenetic protein 2 and cyclooxygenase 2 protein expression in chorioamniotic membranes (R = .34; P < .001).
Conclusion:
Bone morphogenetic protein 2 messenger RNA and protein expression are increased in the chorioamniotic membranes of patients with spontaneous labor at term and patients with preterm labor associated with histologic chorioamnionitis. Its expression pattern and biologic effects strongly suggest that bone morphogenetic protein 2 is involved in human parturition.
