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Steroidogenic Enzyme and Key Decidualization Marker Dysregulation in Endometrial Stromal Cells from Women with Versus Without Endometriosis1
Open accessAbstract
Identification of mechanisms underlying endometriosis pathogenesis will facilitate understanding and treatment of infertility and pain associated with this disorder. Herein, we investigated the expression of steroidogenic pathway enzymes and key decidualization biomarkers in endometrial tissue and in eutopic endometrial stromal fibroblasts (hESFs) from women with vs. those without endometriosis, and subsequently treated in vitro with 8-bromo-cAMP (8-Br-cAMP) or progesterone (P4). Real-time quantitative PCR, immunohistochemistry, ELISA, and radiometric aromatase activity assay were used. The results demonstrate significantly increased (14.5-fold; P=0.037) expression of aromatase in eutopic endometrium of women with disease. In 8-Br-cAMP-treated hESF from eutopic endometrium of women with endometriosis, the balance in estradiol (E2) and P4 biosynthetic and metabolizing enzymes is disturbed (decreased HSD3B1 and HSD17B2, and increased HSD17B1 and aromatase), with the equilibrium being shifted towards an E2-enriched milieu. However, hESF from the same group of women treated with P4 did not demonstrate such responsiveness. Lower expression of IGFBP1 and prolactin mRNA and protein was observed in hESF from women with vs. those without endometriosis in response to 8-Br-cAMP, but not P4, suggesting a blunted response of these decidual biomarkers to activation of the PKA pathway in eutopic endometrium in women with disease. The dichotomy of 8-Br-cAMP regulation of select steroidogenic enzymes leading to an enriched E2 milieu within the endometrium and a blunted response of decidual biomarkers to this decidualizing agent of hESF from women with endometriosis suggests resistance to full decidualization of the stromal fibroblasts and mechanisms underlying implantation failure and the pathophysiology of this disorder.
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In the citing paper
“The fact that hormonal treatments that reduce estradiol levels or influence progesterone alleviate pain in women with endometriosis supports the conclusion that estradiol contributes to pain symptoms and that progestogens may contribute to decreased symptoms (Fedele et al., 2008;Huang, 2008;Aghajanova et al., 2009).”
From Chronic pelvic pain and endometriosis: translational evidence of the relationship and implications (2011) · cites this paper as Aghajanova et al., 2009
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“The expression of the P450 aromatase is increased in adenomyotic tissue and in the ectopic and eutopic endometrium of women with endometriosis [35–41].”
From The pathophysiology of endometriosis and adenomyosis, tissue injury and repair (2009) · cites this paper as [40]
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“The similarity of the molecular biology of TIAR in various tissues with that described in endometriosis [39–41, 59–62] strongly suggests that this represents the common underlying mechanisms of both processes”
From The pathophysiology of endometriosis and adenomyosis, tissue injury and repair (2009) · cites this paper as [40]
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Metadata
- Authors
- Aghajanova, L., Hamilton, A., Kwintkiewicz, J., Vo, K. C., & Giudice, L. C.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Giudice, L.C.
- Venue
- Biology of Reproduction
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-01-01
- Volume
- 80
- Issue
- 1
- Pages
- 105-114
- ISSN
- 0006-3363 (ISSN-L)
- 1529-7268
- PMC
- PMC2704986
- OpenAlex
- W2103654313
- Cited by
- 168
- References
- 78
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 3 · 2023: 5 · 2022: 9 · 2021: 6 · 2020: 11 · 2019: 8 · 2018: 13 · 2017: 11 · 2016: 10 · 2015: 7 · 2014: 8 · 2013: 12 · 2012: 11
- FWCI
- 16.27
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Biology of Reproduction (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- BioOne Complete (BioOne) (submittedVersion)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD055764)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Keywords
- endometriosis, endometrial stromal fibroblasts, decidualization, steroidogenic enzymes, aromatase, estradiol, progesterone, 8-bromo-cAMP, protein kinase A, HSD3B1, HSD17B1, HSD17B2, IGFBP-1, prolactin, implantation failure, eutopic endometrium
- MeSH terms
- Adult, Aromatase, Decidua, Endometriosis, Endometrium, Enzyme-Linked Immunosorbent Assay, Estradiol, Estradiol Dehydrogenases, Female, Humans, Immunohistochemistry, Middle Aged, Progesterone, Prolactin, RNA, Messenger, 8-Bromo Cyclic Adenosine Monophosphate, Stromal Cells, Insulin-Like Growth Factor Binding Protein 1, Reverse Transcriptase Polymerase Chain Reaction, Young Adult
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