Effect of Steroidal Anti-Progestins on Implantation of Fertilized Eggs of Rats and Mice. ∗

Summary

A method for determining the implantation frequency in rats and mice is described: animals found to have mated are autopsied on days 10 to 12 after established mating and the number of implanted fetuses counted. Among animals receiving injections of sesame oil on days 1, 2 and 3 after mating, 13 of 13 rats contained implantations with an average number of 11.5 ± 1.8 fetuses, and 10 of 12 mice were pregnant with an average of 10.2 ± 0.56 fetuses. Significant departures from these frequencies of pregnancy were observed in both rats and mice receiving, on days 1, 2 and 3 in sesame oil as a vehicle, the anti-progestins: 2β, 17β-dihydroxy,2α-ethinyl-A-nor(5α)-androstane (IV); 3β,17β-di-acetoxy,17α - ethinyl − 19 - nor - δ^3,5-androstadiene (VI); 17β-thiomethyl,Δ^1,3,5-16-estratetrene (VIII); and 3,17-dione,19-acetoxy-Δ^1,3-androstadiene (IX). Among 5 other antiprogestins tested (Fig. 1 & Table I) 3 did not significantly reduce the frequency of implantation (I, II and VII) at any dose used in either rats or mice, and 2 (III and V) were active by this criterion in mice but not in rats. In several instances a non-significant reduction in occurrence of implantation was, however, accompanied by a significant reduction in number of implanted fetuses e.g., at low doses in rats receiving IV and VI. A single injection on day 1 after mating of adequate amounts of compounds IV, VI, VIII and IX is effective for implantation inhibition. Injection on day 3 of doses inhibitory when administered on day 1 leads to much less effective implantation inhibition in several instances (Table II). Two compounds (IV and VI) found effective by injection are also effective when given by gavage to rats and mice but higher doses are required for significant effect by this oral route.