Inhibition of Hatching of Mouse Blastocysts in vitro by Prostaglandin Antagonists

The escape of the blastocyst from the zona pellucida in vitro is probably the result of expansion due to fluid accumulation in the blastocoele. This fluid accumulation is mediated by the epithelial trophectoderm. Since prostaglandins of the E series are involved in the control of water movement across epithelia, the effect of prostaglandin antagonists on the hatching of mouse blastocysts has been examined. Protein-free culture media have been used to overcome the complicating effects of protein bindings of the drugs on their activities. 7-Oxa-13-prostynoic acid, meclofenamic acid, indomethacin and pheniodone inhibit hatching, but the properties of their dose-response lines vary. 7-Oxa-13-prostynoic acid and meclofenamic acid have steep dose-response lines. The median inhibitory doses (ID50s) and confidence limits (P = 0.05) are: 7-oxa-13-prostynoic acid 0.81µ M (0.55-1.20); meclofenamic acid 7.72 µM (3.43-17.4). Indomethacin and phenidone have very flat dose-response lines indicating wide variability of response. The ID50s and the confidence limits are: indomethacin 9.08 µM (1-67); phenidone 20 µM (92-263). Thus, 7-oxa-13-prostynoic acid has much greater activity than the other three compounds. The results provide circumstantial evidence that endogenous prostaglandins are involved in blastocyst expansion and may play a role in the process of implantation. Interference with blastocyst expansion with antiprostaglandins administered in a medicated I.U.D. may be a useful means of contraception.