An epigenetic disorder may cause aberrant expression of aromatase gene in endometriotic stromal cells
Open accessAbstract
Objective To examine the molecular basis of aromatase expression in stromal cell culture from endometriotic chocolate cysts.Design Prospective study.Setting Department of Obstetrics and Gynecology and Department of Biosignaling, Tottori University, Yonago Japan.Patient(s) Thirty women, selected randomly, who underwent laparoscopy (n = 18) or laparotomy (n = 12).Intervention(s) Endometrial and endometriotic stromal cells were obtained from the uterus and chocolate cyst lining of the ovary.Main outcome measure(s) Estradiol concentrations in the culture media were measured by means of enzyme immunoassay. Aromatase expression was examined by quantitative real-time polymerase chain reaction. Promoter usage was examined using unique exon I (PII, I.1, I.3, I.4, I.5, and I.6) and exon II primers. To determine the effect of 5-aza-deoxycytidine on endometrial stromal cells, the cells were treated with the agent for 96 hours.Result(s) Endometriotic cells secreted a marginal level of estradiol into the culture media, but adding testosterone to the culture produced a pronounced level of estradiol. In endometrial cells, estradiol production was far less efficient than in endometriotic cells even after adding testosterone. Real-time polymerase chain reaction analyses demonstrated the up-regulation of aromatase messenger RNA (mRNA) expression in endometriotic cells. Three proximal promoters, PII, 1.3, and 1.6, drove mRNA expression. In endometrial cells where a marginal level of aromatase mRNA expression was observed, the same promoters as those in the endometriotic cells were used. To determine the role of epigenetic modification of aromatase gene expression in endometriotic cells, endometrial cells were treated with 5-aza-deoxycytidine, which markedly enhanced aromatase mRNA expression, depending on the same proximal promoters as those in endometriotic cells.Conclusion(s) An epigenetic disorder may play a role in the pathophysiology of endometriosis.
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The promoter of the gene coding for P450 aromatase is hypermethylated and silenced in normal endometrial stromal cells.
“In stark contrast to endometriotic stromal cells, in fact, the promoter of the gene coding for P450 aromatase is hypermethylated in normal endometrial stromal cells, and thus silenced [67,68].”
From The Pathogenesis of Adenomyosis vis-à-vis Endometriosis (2020) · cites this paper as [67]
The difference in E2 production between HESCs and ESCLs is consistent with what has been documented previously.
“The difference in E2 production between HESCs and ESCLs is consistent with what have been documented previously41–45.”
From Platelets induce increased estrogen production through NF-κB and TGF-β1 signaling pathways in endometriotic stromal cells (2020) · cites this paper as [41]
The result of 4.5 fold increase in estrogen production in endometriotic stromal cells stimulated with activated platelets vs. those unstimulated is remarkably close to the reported fold increase found between testosterone-added endometriotic and endometrial stromal cells (4.1 for follicular phase and 4.5 for luteal phase).
“The result of 4.5 fold increase in estrogen production in endometriotic stromal cells stimulated with activated platelets vs. those unstimulated is remarkably close to the reported fold increase found between testosterone-added endometriotic and endometrial stromal cells (4.1 for follicular phase and 4.5 for luteal phase)41.”
From Platelets induce increased estrogen production through NF-κB and TGF-β1 signaling pathways in endometriotic stromal cells (2020) · cites this paper as [41]
Normal endometrial stromal cells only produce negligible levels of estrogens likely due to a silenced aromatase because of hypermethylation.
“While normal endometrial stromal cells only produce negligible levels of estrogens41 likely due to a silenced aromatase because of hypermethylation41,42”
From Platelets induce increased estrogen production through NF-κB and TGF-β1 signaling pathways in endometriotic stromal cells (2020) · cites this paper as [41]
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References 25 · Cited by 83
- Authors
- Izawa, M., Harada, T., Taniguchi, F., Ohama, Y., Takenaka, Y., & Terakawa, N.
- Affiliations
- Tottori University (JP)
- Corresponding author
- Harada, Tasuku
- Venue
- Fertility and Sterility
- Publisher
- Elsevier BV
- Published
- 2008-05
- Volume
- 89
- Issue
- 5
- Pages
- 1390-1396
- ISSN
- 0015-0282 (ISSN-L)
- OpenAlex
- W2038692288
- Cited by
- 83
- References
- 25
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 9 · 2022: 3 · 2021: 1 · 2020: 7 · 2019: 3 · 2018: 3 · 2017: 5 · 2016: 6 · 2015: 5 · 2014: 7 · 2013: 5 · 2012: 4
- FWCI
- 5.50
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Fertility and Sterility (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- endometriosis, aromatase, endometriotic stromal cells, endometrial stromal cells, epigenetic regulation, promoter usage, estradiol production, 5-aza-deoxycytidine, DNA methylation, endometrioma, aromatase mRNA expression
- MeSH terms
- Decitabine, Aromatase, Azacitidine, Cells, Cultured, Endometriosis, Estradiol, Female, Humans, Ovarian Diseases, Promoter Regions, Genetic, RNA, Messenger, Uterine Diseases, Gene Expression Regulation, Enzymologic, Stromal Cells, CpG Islands, DNA Methylation, Epigenesis, Genetic
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