Aberrant expression and localization of deoxyribonucleic acid methyltransferase 3B in endometriotic stromal cells
Open accessAbstract
Objective To define the expression and function of DNA methyltransferases (DNMTs) in response to decidualizing stimuli in endometriotic cells compared with healthy endometrial stroma.Design Basic science.Setting University research center.Patient(s) Premenopausal women with or without endometriosis.Intervention(s) Primary cultures of stromal cells from healthy endometrium (E-IUM) or endometriomas (E-OSIS) were subjected to in vitro decidualization (IVD) using 1 μM medroxyprogesterone acetate, 35 nM 17β-estradiol, and 0.05 mM 8-Br-cAMP.Main outcome measure(s) Expression of DNMT1, DNMT3A, and DNMT3B in E-IUM and E-OSIS were assessed by quantitative real-time polymerase chain reaction and immunoblotting. Recruitment of DNMT3B to the promoters of steroidogenic factor 1 (SF-1) and estrogen receptor α (ESR1) was examined by chromatin immunoprecipitation.Result(s) IVD treatment reduced DNMT3B messenger RNA (74%) and protein levels (81%) only in E-IUM; DNMT1 and DNMT3A were unchanged in both cell types. Significantly more DNMT3B bound to the SF-1 promoter in E-IUM compared with E-OSIS, and IVD treatment reduced binding in E-IUM to levels similar to those in E-OSIS. Enrichment of DNMT3B across 3 ESR1 promoters was reduced in E-IUM after IVD, although the more-distal promoter showed increased DNMT3B enrichment in E-OSIS after IVD.Conclusion(s) The inability to downregulate DNMT3B expression in E-OSIS may contribute to an aberrant epigenetic fingerprint that misdirects gene expression in endometriosis and contributes to its altered response to steroid hormones.
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- Authors
- Dyson, M. T., Kakinuma, T., Pavone, M. E., Monsivais, D., Navarro, A., Malpani, S. S., Ono, M., & Bulun, S. E.
- Affiliations
- Northwestern University (US)
- Corresponding author
- Dyson, Matthew T.
- ORCID
- Venue
- Fertility and Sterility
- Publisher
- Elsevier BV
- Published
- 2015-10
- Volume
- 104
- Issue
- 4
- Pages
- 953-963.e2
- ISSN
- 0015-0282 (ISSN-L)
- PMC
- PMC4603532
- OpenAlex
- W1685873630
- Cited by
- 37
- References
- 74
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 3 · 2022: 4 · 2021: 3 · 2020: 2 · 2019: 7 · 2018: 2 · 2017: 3 · 2016: 5
- FWCI
- 3.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Fertility and Sterility (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R37-HD038691)
- National Institute of Child Health and Human Development (U54-HD40093)
- Friends of Prentice Grants Initiative
- American Society for Reproductive Medicine
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Keywords
- DNMT3B, endometriosis, endometrial stromal cells, decidualization, DNA methylation, epigenetics, steroidogenic factor 1, estrogen receptor alpha, promoter binding, endometrioma, medroxyprogesterone acetate, estradiol, 8-bromo-cAMP
- MeSH terms
- DNA Methyltransferase 3B, Adult, Cells, Cultured, DNA (Cytosine-5-)-Methyltransferases, Endometriosis, Endometrium, Female, Humans, Middle Aged, Ovarian Diseases, Embryo Implantation, Tissue Distribution, Gene Expression Regulation, Enzymologic, Stromal Cells
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