Abstract
Objective:
Several matrix metalloproteinases (MMP) have been implicated in preterm parturition. We hypothesized that administration of a MMP inhibitor would reduce the rate of inflammation-mediated preterm delivery and prolong gestation in a mouse model.

Study design:
We utilized an animal model of endotoxin-induced preterm delivery using timed pregnant C57Bl6 mice. Test animals received lipopolysaccharide (LPS) followed by the MMP inhibitor at 1 dose 12 hours after the LPS. Control mice received the same dose of LPS, followed by a control solution 12 hours after the LPS. The primary outcome was preterm delivery rate.

Results:
Mice in the study group had a significantly lower rate of preterm delivery (44%) compared to 100% in the controls (P=.009). Furthermore, the latency between the administration of injection and delivery was also longer in the study group (mean 28.3 hours, standard deviation 9.4 hours) than among controls (mean 15.7 hours, standard deviation 1.8 hours) (P<.001).

Conclusion:
Administration of an MMP inhibitor results in a decreased rate of inflammation-mediated preterm delivery in this animal model (Fig 1).
 

Figure 1: Effect of MMP inhibition on lipopolysaccharide-induced preterm delivery. Ten mice were treated on E15.5-E16 with lipopolysaccharide, followed by vehicle (squares). Another 10 mice were treated with lipopolysaccharide, followed by MMP inhibitor (triangles). Statistical analysis, using the Fisher exact test, showed a significant difference (P=.009) in the effect of LPS in inducing preterm labor between mice treated with LPS followed by control solution and mice treated with LPS followed by the MMP inhibitor solution. Statistical analysis using the Mann-Whitney test, showed a significant prolongation (P=.001) of the injection-to-delivery interval. (Reprinted from Koscica KL, Ananth CV, Placido J, et al. The effect of a matrix metalloproteinase inhibitor on inflammation-mediated preterm delivery. Am J Obstet Gynecol. 2007;196:551.e1-551.e3, with permission from Elsevier.)