Endometrial and Myometrial Effects of Progesterone Antagonists in Pregnant Guinea Pigs
Antiprogestins of the RU 486 type (RU 486, ZK 98 734, ZK 98 299) were studied at different stages of pregnancy in the guinea pig. Treatment starting on day 4 postconception was able to prevent nidation completely, all compounds had comparable inhibitory potency. Treatment after nidation, starting on day 8 postconception induced decidual collapse and bleeding; however, embryonic tissue was retained in nidation sites. Luteolysis, as opposed to animals in nonfertile cycles, was not induced, indicating a lack of ability of antiprogestins to induce uterine prostaglandin synthesis/liberation. On day 43 postconception there was marginal abortifacient activity of RU 486. The other compounds induced expulsion more rapidly and at a higher rate. The comparatively pronounced antiglucocorticoid activity of RU 486 may account for this difference. High uterine prostaglandin sensitivity and a cervical ripening were induced consistently; fast, spontaneous labor, on the other hand, occurred after several days if at all. Complete uterine evacuation was induced within hours by otherwise inactive doses of Sulprostone in various combinations with ZK 98 299 and RU 486, but surprisingly not with ZK 98 734. A single dose of ZK 98 299 induced an approximately 30-fold increase in uterine prostaglandin sensitivity within 24 h, exceeding that present preterm, but no spontaneous labor.