Induction of preterm labor in the rabbit by antiprogesterone

On the 25th day of pregnancy, 14 New Zealand white rabbits were treated orally with 500 mg of the progesterone (P)-synthesis inhibitor: Isoxazol. This treatment was repeated 12 hours (n = 6) or 24 hours (n = 8) later. An additional group of 6 rabbits received at the same time the solvent, without Isoxazol, to serve as vehicle controls. From day 26 onward all these 20 animals were induced every day with a single i.v. injection of 100 mU oxytocin until they delivered. The 14 Isoxazol rabbits responded to oxytocin on day 27.7 plus or minus 0.2 (Mean plus or minus S.E.), while the vehicle controls failed to respond until day 30.3 plus or minus 0.4 of pregnancy (p smaller than 0.001). Progesterone assays in the uterine vein plasma showed that, in comparison with 14 untreated controls of similar gestational age, plasma P of the 14 Isoxazol rabbits was significantly reduced (p smaller than 0.01). The vehicle controls became inducable when their P was endogenously lowered to the level at which oxytocin readily provokes parturition near term. Neither Isoxazol, nor oxytocin altered the normally low prostaglandin F levels of the uterine vein plasma, indicating that Isoxazol provokes premature inducability in the rabbit through P-withdrawal, rather than through an elevation of PG-levels.