Promoter Hypermethylation of Progesterone Receptor Isoform B (PR-B) in Adenomyosis and Its Rectification by a Histone Deacetylase Inhibitor and a Demethylation Agent

Jichan Nie, Xishi Liu, Sun-Wei Guo, Sun‐Wei Guo
Reproductive sciences (Thousand Oaks, Calif.) · 2010 · vol. 17(11) , pp. 995–1005 · doi:10.1177/1933719110377118 · PMID:20697142 · W1985706154
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⚙ AI-generated summary by claude@2026-06+body, 2026-06-06 ⓘ

Adenomyosis exhibits PR-B promoter hypermethylation, which can be reversed by TSA and ADC, decreasing cell viability and suppressing cell cycle progression in ectopic endometrial stromal cells.

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The study investigated whether the promoter of progesterone receptor isoform B (PR-B) is hypermethylated in adenomyosis and assessed, using ectopic and normal endometrial stromal cells, whether the histone deacetylase inhibitor trichostatin A (TSA) and the demethylation agent 5-aza-2-deoxycytidine (ADC) alter PR-B gene/protein expression and ectopic cell viability. Ectopic stromal cells came from 9 women with adenomyosis and control stromal cells from 8 women with benign ovarian cysts without clinical history of endometriosis/adenomyosis/myoma, and analyses included methylation-specific PCR, RT-PCR, Western blot, viability assays, and flow cytometry. PR-B promoter methylation was absent in normal stromal cells but present in 2 of 3 ectopic stromal cell preparations, while TSA and ADC increased PR-B expression in ectopic but not normal cells and reduced viability dose-dependently, alongside suppression of cell cycle progression. The caveat is the small sample size and that only ectopic cell preparations were shown to have methylation in a subset (2/3). This paper is centrally about adenomyosis — it links PR-B promoter hypermethylation in adenomyosis to pharmacologic “rectification” by TSA and ADC, with mechanistic effects on ectopic stromal cell viability.

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Abstract

Adenomyosis is a fairly common gynecologic disease with unknown pathogenesis. We sought to investigate as to whether the promoter of progesterone receptor isoform B (PR-B) is hypermethylated in adenomyosis and to investigate the treatment of ectopic endometrial stromal cells with trichostatin A (TSA), a histone deacetylase inhibitor (HDI), and 5-aza-2-deoxycytidine (ADC), a demethylation agent, on PR-B gene and protein expression, and on cell viability. Ectopic endometrial tissue specimens were obtained from 9 women with adenomyosis whereas control endometrial tissue samples were obtained from 8 women with surgically diagnosed benign ovarian cysts but without any clinical history of endometriosis/adenomyosis/myoma. Endometrial stromal cells were isolated, purified, cultured, and analyzed by methylation-specific polymerase chain reaction (PCR), real-time reverse transcriptase PCR (RT-PCR), and Western blot analysis, cell viability assays, and fluorescence-activated cell sorting. We found that none of the normal endometrial stromal cells had PR-B promoter methylation. In contrast, 2 out of 3 ectopic endometrial stromall cells had PR-B hypermethylation (P <.05). The treatment with both TSA and ADC elevated PR-B gene and protein expression in ectopic, but not in normal, endometrial stromal cells. Both TSA and ADC treatment dose-dependently reduced cell viability of ectopic endometrial stromal cells. Trichostatin A and ADC treatment also suppressed the cell cycle progression in ectopic endometrial stromal cells. Thus, this study provides the first piece of evidence that adenomyosis has epigenetic aberration and may also be an epigenetic disease amenable to rectification by pharmacological means. This perspective may shed new light onto the pathogenesis of adenomyosis and lead to novel ways to treat the disease. Similar content being viewed by others

References

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mesh:D004715adenomyosis

MeSH descriptors

DNA Modification Methylases Endometriosis Enzyme Inhibitors Histone Deacetylase Inhibitors Promoter Regions, Genetic Receptors, Progesterone Receptors, Progesterone Azacitidine Azacitidine Azacitidine Cells, Cultured Decitabine DNA Modification Methylases Endometriosis Endometriosis Endometrium Endometrium Endometrium Endometrium Enzyme Inhibitors

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