Abstract
Human preimplantation embryos secrete platelet‐activating factor (PAF), which stimulates prostaglandin E~2~ synthesis from secretory endometrium. This study investigated the action of PAF on phosphatidylinositol 4,5‐bisphosphate (Ptdlns(4,5)P~2~)‐specific phospholipase C activity in human endometrium. Slices of normal endometrium were incubated with 5 μCi/ml myo‐[2‐^3^H] inositol for 3 h at 37°C in 95% O~2~ and 5% CO~2~ to label tissue phosphoinositides. Inositol phosphates were extracted using trichloroacetic acid precipitation and diethylether neutralization and production was measured using Dowex 1‐X8 anion‐exchange column chromatography. PAF induced rapid and concentration‐dependent accumulation of inositol phosphates (IP) from secretory endometrium, but had no effect on endometrium removed in the proliferative phase of the menstrual cycle. The IP~3~ fraction was significantly elevated from a median value of 14.0 c.p.m. mg^−1^ dry wt [range: 8–41 c.p.m. mg^−1^ dry wt] to 28.0 c.p.m. mg^−1^ dry wt [range: 11–87 c.p.m. mg^−1^ dry wt, P < 0.002] following 1 min exposure of secretory endometrium to PAF‐acether, in the presence of 10 mM LiCl. PAF‐induced hydrolysis of Ptdlns(4,5)P~2~ was inhibited by the specific PAF receptor antagonist WEB 2086, in a dose‐dependent manner (P < 0.02), indicating that in human endometrium Ptdlns(4,5)P~2~ hydrolysis is mediated via a PAF receptor. These results indicate that PAF receptor coupling activates endometrial Ptdlns(4,5)P~2~‐specific phospholipase C only in the secretory phase of the menstrual cycle, suggesting that the PAF response may be under ovarian steroid regulation. It is proposed that the ability of the endometrium to respond to PAF appears to be a feature of the preparation of this tissue for implantation and that the second messengers generated may play a role in cellular processes involved in the maternal recognition of very early human pregnancy. © 1992 Wiley‐Liss, Inc.