ANORDIOL AND RU486 SYNERGIZE TO PRODUCE PREIMPLANTATION PREGNANCY LOSS BY INCREASING EMBRYO TRANSPORT (RAT)

RU486, an antiprogestational agent, and anordiol (dihydroxylated metabolite of anordrin) which has an estrogenic and antiestrogenic activity, are known to inhibit fertility. These agents were administered orally, alone or together, to rats prior to implantation, on Day 2 of pregnancy. Control animals were fed with the vehicle only. The effectiveness of the agents in terminating pregnancy in female rats was determined on Day 14 of pregnancy. Anordiol presented a dose-dependent effect on abolishing pregnancy, being 100% effective at 2.5 mg/Kg and non-effective at 0.6 mg/Kg. RU486 did not prevent pregnancy even at a dose of 4 mg/Kg. Doses of RU486 and anordiol that were ineffective when administered alone, prevented pregnancy in 70% of the rats when these agents were given together. To determine the mechanism by which these drugs prevent pregnancy, oviducts and uteri of rats were examined for presence of embryos on Day 3 of pregnancy. Only 29% of embryos were recovered from the oviducts of rats treated with 2.5 mg/Kg anordiol (compared to 89% in control group) plus an additional 9% from the uteri. In combination, anordiol and RU486 had a synergistic effect on embryo transport in the rats' reproductive tract, without any apparent accumulation in the uterus. These results led us to conclude that the pregnancy preventing action of anordiol plus RU486 is mostly due to accelerated transport of the embryos in the reproductive tract prior to implantation.