Role of Histamine in Implantation: Dexamethasone Inhibits Estradiol-Induced Implantation in the Rat1
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.
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Mast cell degranulation releases histamine, MMPs, tryptase and VEGF, which are involved in the attachment and posterior invasion of the embryo into the uterus.
“their degranulation causes the release of pivotal factors, e.g., histamine, MMPs, tryptase and VEGF, which are known to be involved in the attachment and posterior invasion of the embryo into the uterus.”
From Estradiol and Progesterone Regulate the Migration of Mast Cells from the Periphery to the Uterus and Induce Their Maturation and Degranulation (2010) · cites this paper as [2]
Uterine-derived histamine is a key regulator in implantation due to its ability to alter uterine vascular permeability and induce stromal decidualization.
“Uterine-derived histamine has long been suspected as a key regulator in implantation due to its ability of altering uterine vascular permeability and inducing stromal decidualization [2].”
From Estradiol and Progesterone Regulate the Migration of Mast Cells from the Periphery to the Uterus and Induce Their Maturation and Degranulation (2010) · cites this paper as [2]
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- Authors
- Johnson, D. C., & Dey, S. K.
- Affiliations
- University of Kansas Medical Center (US)
- Venue
- Biology of Reproduction
- Publisher
- Oxford University Press (OUP)
- Published
- 1980-06-01
- Volume
- 22
- Issue
- 5
- Pages
- 1136-1141
- ISSN
- 0006-3363 (ISSN-L)
- 1529-7268
- OpenAlex
- W2409854994
- Cited by
- 74
- References
- 0
- Citations by year
- 2023: 1 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 1 · 2017: 5 · 2015: 3 · 2014: 2 · 2013: 4 · 2012: 1
- FWCI
- 1.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biology of Reproduction (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Keywords
- histamine, implantation, dexamethasone, estradiol, progesterone, delayed implantation, prostaglandin E2, glucocorticoids, prostaglandin synthesis, endometrial receptivity
- MeSH terms
- Animals, Blastocyst, Dexamethasone, Estradiol, Estrogen Antagonists, Female, Histamine, Hypophysectomy, Embryo Implantation, Rats
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