The degenerative effect on rabbit implantation sites by indomethacin. I. Timing of indomethacin action, possible effect on uterine proteins and the effect of replacement doses of PGF2 alpha.

To determine the effective time of indomethacin (Id) action in disrupting early pregnancy, groups of rabbits were treated at various stages after mating with Id and/or replacement doses of PGF2 alpha. Effect of Id on the secretion of uterine proteins was also investigated. The highest rate of embryonic death occurred when Id was injected twice daily during days 5-7 of pregnancy, and days 5-6 appear to be the most critical. Persisting levels of Id during this critical stage is required to induce the antifertility effect. The results also indicate that the adverse effect of Id is not mediated through an effect on uterine proteins, and is mainly due to the inhibition of PG's synthesis. PG's are apparently required for normal implantation and early development.