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

RU486, an antiprogestational agent, and anordiol (dihydroxylated metab olite of anordrin) which has an estrogenic and antiestrogenic activity , are known to inhibit fertility. These agents were administered orall y, alone or together, to rats prior to implantation, on Day 2 of pregn ancy. Control animals were fed with the vehicle only. The effectivenes s 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-effec tive 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 adminis tered alone, prevented pregnancy in 70% of the rats when these agents were given together. To determine the mechanism by which these drugs p revent pregnancy, oviducts and uteri of rats were examined for presenc e 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 t o 89% in control group) plus an additional 9% from the uteri. In combi nation, anordiol and RU486 had a synergistic effect on embryo transpor t in the rats' reproductive tract, without any apparent accumulation i n the uterus. These results led us to conclude that the pregnancy prev enting action of anordiol plus RU486 is mostly due to accelerated tran sport of the embryos in the reproductive tract prior to implantation.