Histamine enhances cytotrophoblast invasion by inducing intracellular calcium transients through the histamine type-1 receptor.
Abstract
Blastocyst implantation and placentation require molecular and cellular interactions between the uterine endometrium and blastocyst trophectoderm. Previous studies showed that histamine produced in the mouse uterine luminal epithelium interacts with trophoblast histamine type-2 receptors (H2) to initiate blastocyst implantation. However, it is unknown whether similar histamine activity is operative in humans. Using a human cell line (HTR-8/SVneo) derived from first-trimester cytotrophoblasts that expresses both histamine type-1 receptor (H1) and H2, we found that histamine promotes cytotrophoblast invasiveness specifically through activation of H1. Stimulation of H1 in human cytotrophoblasts by histamine induced intracellular Ca2+ (Ca(2+)i) transients by activating phospholipase C and the inositol trisphosphate pathway. The enhanced invasion induced by histamine was blocked by pretreatment with H1 antagonist or by chelation of Ca(2+)i. These findings suggest possible differences between rodents and humans in histamine signaling to the trophoblast.
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Histamine is produced mainly by mast cells that are present in both the uterus and placenta.
“Histamine is produced mainly by MCs that are present in both the uterus and placenta [3].”
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 [3]
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Background
- Authors
- Liu, Z., Kilburn, B. A., Leach, R. E., Romero, R., Paria, B. C., & Armant, D. R.
- Affiliations
- Wayne State University (US)
- United States Department of Health and Human Services (US)
- Vanderbilt University Medical Center (US)
- Corresponding author
- Armant, D. Randall
- Venue
- Molecular Reproduction and Development
- Publisher
- Wiley
- Published
- 2004-04-21
- Volume
- 68
- Issue
- 3
- Pages
- 345-353
- ISSN
- 1040-452X (ISSN-L)
- 1098-2795
- OpenAlex
- W2079111092
- Cited by
- 24
- References
- 44
- Citations by year
- 2026: 2 · 2025: 1 · 2022: 2 · 2019: 2 · 2017: 1 · 2015: 1 · 2014: 1 · 2013: 1 · 2012: 3
- FWCI
- 0.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Reproduction and Development (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (HD 037394, HD36764, AA12057, HD98004, HD37500)
- Perinatology Research Branch, Intramural Division, National Institute of Child Health and Human Development (National Institutes of Health
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Keywords
- histamine, cytotrophoblast invasion, calcium transients, phospholipase C, HTR-8/SVneo cells, embryo implantation, placentation, endometrium, trophoblast
- MeSH terms
- Calcium, Cell Adhesion, Cells, Cultured, Egtazic Acid, Histamine, Histamine H1 Antagonists, Humans, Isoquinolines, Embryo Implantation, Phosphatidylinositols, Type C Phospholipases, Receptors, Histamine H1, Receptors, Histamine H2, Sulfonamides, Trophoblasts, Calcium Signaling, Cell Proliferation
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