Role of Histamine in Implantation: Dexamethasone Inhibits Estradiol-Induced Implantation in the Rat

Abstract

Delayed implantation was achieved by injecting progesterone (2 mg/day) into pregnant rats hypophysectomized 48 to 72 h after spermatozoa were found in vaginal flushings. A single i.v. dose of 20 ng (≅ 80 ng/kg BW) of estradiol (E₂) induced a full complement of implantation sites (6.0 ± 0.32 sites/uterine horn) in all animals. A dose of 40 ng/kg of E₂ was the minimal dose which induced implantation in all animals; the number of sites, however, was reduced by 50%. A normal number of implantation sites was obtained when histamine dihydrochloride (histamine) was injected i.p. at the same time E₂ was given. The number of animals with sites and the number of sites increased in rats given one dose of histamine plus 30, but not 20, ng/kg of E₂. Three doses of histamine given at 4 h intervals augmented 20 ng/kg of E₂ and induced implantation in 87% of the rats. Dexamethasone administered s.c. for 4 days inhibited implantation in 80% of the rats given E₂ but this could be overcome by injection of two doses of histamine. Injection of dexamethasone simultaneously with E₂ had no effect, and when given up to 4 h before E₂ had little effect upon implantation. However, when given 6 h or more before E₂, the glucocorticoid drastically reduced both the number of animals with implantation sites and the number of sites. The inhibition induced by 6 h of exposure to dexamethasone could be completely reversed by administration of three doses (250 µg each) of prostaglandin E₂ (PGE₂). With longer exposure to the corticoid this amount of PGE₂ was less effective. Extrapolating the effects of anti-inflamatory glucocorticoids in other tissues, we suggest that at least part of the effect of histamine in augmenting implantation induced by estrogen involves an increase in prostaglandin synthesis.