Dose response of RU486 in a novel rabbit model of noninfectious preterm birth: Comparative efficacy of 3 routes of administration

• Published in: American journal of obstetrics and gynecology Vol. 192; no. 3; pp. 924 - 931
• Main Authors: Gorenberg, David, Beharry, Kay, Nishihara, Kenji C., Chang, Eileen, Waltzman, Joshua, Akmal, Aamir, Asrat, Tamerou
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA Mosby, Inc 01-03-2005; Elsevier
• Subjects: Abortifacient Agents, Steroidal - administration & dosage; Animals; Biological and medical sciences; Cortisol; Cytokine; Cytokines - analysis; Disease Models, Animal; Female; Gynecology. Andrology. Obstetrics; Hydrocortisone - analysis; Injections, Intramuscular; Injections, Intraperitoneal; Injections, Subcutaneous; Medical sciences; Mifepristone - administration & dosage; Pregnancy; Premature Birth - chemically induced; Preterm birth; Progesterone; Progesterone - analysis; Rabbit; Rabbits; Rabbit; Cortisol; Preterm birth; Progesterone; Cytokine; Animal model; Pregnancy disorders; Hydrocortisone; Route of administration; Glucocorticoid; Progestagen; Dose activity relation; Corticosteroid; Steroid hormone; Treatment efficiency; Gynecology; Antiinflammatory agent; Premature delivery; Lagomorpha; Obstetrics; Ovarian hormone; Cortisol Cytokine Preterm birth Progesterone Rabbit; Vertebrata; Mammalia; Prematurity; Animal; Adrenal hormone; Sex steroid hormone; Comparative study
• ISSN: 0002-9378; 1097-6868
• DOI: 10.1016/j.ajog.2004.11.061

The purpose of this study was to examine whether the pregnant rabbit model can be used as a viable model for the study of non–infection-mediated preterm birth.
Timed pregnant New Zealand rabbits were injected with a single dose of RU486 on day 22 of gestation. Three doses (50 mg, 75 mg, and 100 mg) were administered intramuscularly, intraperitoneally, or subcutaneously. The rabbits were monitored for preterm delivery. Progesterone, cortisol, and cytokine levels were examined before the induction and after delivery. Uterine and cervical progesterone, cortisol, and cytokine levels were determined after delivery.
RU486 resulted in 100% preterm delivery in all doses and modes of administration, compared with 0% of controls. Intramuscular administration appeared to generate the most favorable preterm delivery time. Rabbits that received 100 mg RU486 intramuscularly showed significantly decreased serum progesterone levels and uterine progesterone levels, compared with 100 mg subcutaneously and intraperitoneally.
RU486 that was administered intramuscularly appears to be a potent and effective method for inducing preterm birth. This model of hormonally mediated preterm birth might serve as a useful model for the investigation of the possible mechanisms of preterm labor.