The role of arachidonic acid and/or its metabolites in embryo implantation initiated by epidermal growth factor (EGF).

Previous studies have shown that epidermal growth factor (EGF) can replace estrogen for initiating embryo implantation in hypophysectomized rats in which pregnancy was maintained with progesterone, provided that uterine trauma preceded the intravenous dose of the growth factor. The present study has shown that intraperitoneal administration of prostaglandin E2 (PGE2) or histamine dihydrochloride can replace the need for uterine trauma. On the other hand, indomethacin (1 mg subcutaneous), an inhibitor or prostaglandin synthase (PGHS) and phospholipase A2 (PLA2) inhibited the implantation initiated by EGF plus trauma or even EGF plus PGE2, but had no effect upon that initiated by estradiol. A much larger dose of another PGHS inhibitor, ibuprofen, did not inhibit, but appeared to enhance, the effect of EGF plus trauma. The lipoxygenase inhibitor nordihydroguairaretic acid also was ineffective at inhibiting the action of EGF plus trauma. In contrast to the ineffectiveness of these non-steroidal anti-inflammatory agents, the synthetic glucocorticoid dexamethasone inhibited implantation initiated by either EGF or estradiol. These results are consistent with the interpretation that treatment with agents known to inhibit the activity of PLA2, and thus availability of arachidonic acid, are more potent inhibitors of implantation initiated by EGF than those that only inhibit PGHS.