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106: Progestational agents, prostaglandins and preterm cervical ripening: Critical pathways for preterm parturition

      Objective

      Progestational agents (PAs) have been demonstrated to decrease the rates of preterm birth (PTB) in high risk patients—most recently in patients with short cervices. The molecular mechanisms by which PAs prevent PTB—or more specifically cervical ripening are not understood. Prostaglandins (PGs) play a fundamental and complex role in parturition and cervical ripening. This study sought to determine if inflammation-induced PTB and/or PAs altered expression or regulation of mediators in the PG pathway in the cervix.

      Study Design

      E15 CD-1 mice were randomized to 1) intrauterine infusion of saline 2) intrauterine infusion of LPS and 3) pretreatment with medroxyprogesterone acetate (MPA) (1mg/dam) 1 hour prior to intrauterine LPS. Cervices were harvested at 6 hrs for QPCR. In a separate set of experiments, E15 mice were randomized to MPA (1mg/dam) or vehicle and cervices were harvested at 24 hrs QPCR or for immunohistochemistry.

      Results

      LPS and MPA significantly altered PG expression (TABLE). MPA alone induced the expression of Hpgd, EP2 and EP4 in the absence of inflammation. Hpgd protein expression was decreased by LPS and increased in cervical stroma by MPA.

      Conclusion

      Intrauterine inflammation can effect PG metabolism in the cervix possibly leading to preterm cervical ripening. The ability of PAs to modulate this effect may be a critical mechanism by which PAs prevent PTB in women with short cervices. This study suggests that exogenous administration of PAs during pregnancy can forestall the natural process of cervical ripening through modulation of the PG pathway in the cervix.