Capillary permeability changes in the uteri of recipient rabbits after transfer of blastocysts from indomethacin-treated donors.

Blastocysts recovered from control or indomethacin-treated (10 mg/kg s.c. twice daily starting on Day 4.5 of pregnancy) donor rabbits were transferred to the uteri of Day-6 or 6.5 pseudopregnant recipients. The minimal time required to cause an increase in capillary permeability in the endometrium underlying control blastocysts was approximately 9 h. Blastocysts derived from the indomethacin-treated donors were depleted of PGE and PGF (determined by RIA) and were unable to produce any increase in capillary permeability during the same time period, although after 46 h in vivo the diameters of the implantation swellings related to control or indomethacin-treated blastocysts were not different. This suggests that, in the untreated recipients, blastocysts depleted of PGs can become replenished and then release these PGs in a site-directed manner. Indomethacin thus causes a delay rather than a complete inhibition of implantation. Incubation of the indomethacin-treated blastocysts in vitro led to replenishment with PGs, but such replenished blastocysts failed to induce an increase in capillary permeability within the same time-frame as control blastocysts. Evidence is presented that indomethacin is probably not the cyclooxygenase inhibitor of choice, since it interferes with PG uptake and efflux. Such an action could explain the failure of the replenished blastocysts to induce a normal increase in capillary permeability.