Reduced expression of progesterone receptor-B in the endometrium of women with endometriosis and in cocultures of endometrial cells exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin
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Objective To analyze endometrial progesterone receptor (PR) expression in women with endometriosis compared with disease-free women and to assess the impact of in vitro 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure on PR isotype expression.Design Controlled laboratory study.Setting University medical center.Patient(s) Healthy volunteers and women with surgically diagnosed endometriosis.Intervention(s) None.Main outcome measure(s) Analysis of in vivo PR-A and PR-B expression in endometrium from women with and without endometriosis. The impact of in vitro TCDD exposure on PR-B/PR-A ratio and cell-specific matrix metalloproteinase (MMP) expression was also determined.Result(s) The PR-B/PR-A ratio was lower in endometrial tissues from women with endometriosis compared with normal tissues. A similar ratio was induced in normal stromal cells cocultured with epithelial cells and exposed to TCDD. Disruption of stromal PR expression following TCDD exposure was associated with a failure of P-mediated down-regulation of both stromal-specific pro-MMP-3 and epithelial-specific pro-MMP-7.Conclusion(s) Our data suggest that reduced progesterone (P) sensitivity in the endometrium of women with endometriosis may be related to an altered pattern of PR expression. The ability of TCDD to selectively down-regulate stromal PR-B expression and increase MMP expression in both stromal and epithelial cells suggests that exposure to this toxin may negatively impact P-mediated cell-cell communication in the human endometrium.
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A decreased PR-B/PR-A ratio has been demonstrated in ectopic tissue and in eutopic endometrium of women with endometriosis, albeit not consistently.
“A decreased PR-B/PR-A ratio has been demonstrated not only in ectopic tissue (Attia et al., 2000), but also in eutopic endometrium of women with endometriosis (Igarashi et al., 2005), albeit not consistently (Bukulmez et al., 2008).”
From “Waiting for Godot”: a commonsense approach to the medical treatment of endometriosis (2011) · cites this paper as Igarashi et al., 2005
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Self-citation
- Authors
- Igarashi, T. M., Bruner-Tran, K. L., Yeaman, G. R., Lessey, B. A., Edwards, D. P., Eisenberg, E., & Osteen, K. G.
- Affiliations
- Vanderbilt University (US)
- Prisma Health (US)
- University of Colorado Health (US)
- Corresponding author
- Osteen, Kevin G.
- Venue
- Fertility and Sterility
- Publisher
- Elsevier BV
- Published
- 2005-07
- Volume
- 84
- Issue
- 1
- Pages
- 67-74
- ISSN
- 0015-0282 (ISSN-L)
- OpenAlex
- W2134753968
- Cited by
- 163
- References
- 57
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 3 · 2023: 6 · 2022: 9 · 2021: 6 · 2020: 5 · 2019: 5 · 2018: 7 · 2017: 10 · 2016: 7 · 2015: 7 · 2014: 8 · 2013: 13 · 2012: 10
- FWCI
- 8.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Fertility and Sterility (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Funders
- Vanderbilt University
- National Institutes of Health
- School of Medicine, Vanderbilt University
- National Institute of Environmental Health Sciences (R21ES12298, R21ES012298)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD037321, U54 HD37321)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Keywords
- endometriosis, progesterone receptor B, progesterone receptor A, endometrium, 2,3,7,8-tetrachlorodibenzo-p-dioxin, endocrine disruptors, matrix metalloproteinase-3, matrix metalloproteinase-7, endometrial stromal cells, intercellular communication
- MeSH terms
- Polychlorinated Dibenzodioxins, Adult, Cells, Cultured, Endometriosis, Endometrium, Female, Gene Expression Regulation, Humans, Receptors, Progesterone, Stromal Cells, Statistics, Nonparametric, Coculture Techniques, Matrix Metalloproteinases
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