A MODEL FOR INVESTIGATING MICROSCOPIC CHANGES INDUCED BY PROSTAGLANDIN-E(2) IN THE TERM CERVIX

Objective: The purposes of this study were twofold: to examine microscopic changes in the term cervix after prostaglandin E2 (PGE2) using the rabbit model, and to determine the lowest dose of PGE2 that would consistently prompt microscopic change as a basis for future investigation. Methods: Twenty-four New Zealand white rabbits were administered either a placebo or PGE2 gel using hysteroscopic guidance in a blind randomized manner. Twelve served as placebo gel-treated controls-six at 27 days of gestation and six at 29 days, shortly before the anticipated time of early labor. Prostaglandin E2 gel was instilled in the remaining 12 rabbits at day 27 using either a 0.04 mg/kg or 0.08 mg/kg dose which are the human body weight equivalents for cervical ripening. Microscopic changes in the cervix were evaluated by two pathologists in a blind manner, then compared using analyses of variance testing. Results: Compared with the day 27 control group, microscopic changes in the day 29 control group were more apparent for the presence of submucosal edema (P = 0.03), dissolution of collagen bundles (P = 0.01), and presence of multinucleated histiocytes (P = 0.001). Microscopic changes in the cervix after use of the higher prostaglandin E2 dose on day 27 were more apparent than after using the lower dose and were indistinguishable from the day 29 controls. Conclusion: Using the gravid rabbit near term, PGE2 applied near the cervical os stimulated in a dose-dependent manner the same microscopic changes in the cervical connective tissue as those found during early labor. These findings using the 0.08 mg/kg dose should serve in future investigations to answer clinical questions pertaining to cervical ripening.