Aberrant Endometrial DNA Methylome and Associated Gene Expression in Women with Endometriosis
Open accessAbstract
Endometriosis is an estrogen-dependent, progesterone-resistant disorder largely derived from retrograde transplantation of menstrual tissue/cells into the pelvis, eliciting an inflammatory response, pelvic pain, and infertility. Eutopic endometrium (within the uterus), giving rise to pelvic disease, displays cycle-dependent transcriptomic, proteomic, and signaling abnormalities, and although its DNA methylation profiles dynamically change across the cycle in healthy women, studies in endometriosis are limited. Herein, we investigated the DNA methylome and associated gene expression in three phases of the cycle in eutopic endometrium of women with severe endometriosis versus controls, matched for ethnicity, medications, smoking, and no recent contraceptive steroid use. Genome-wide DNA methylation and gene expression were coassessed in each sample. Cycle phase was determined by histology, serum hormone levels, and unsupervised principal component and hierarchical cluster analyses of microarray data. Altered endometrial DNA methylation in endometriosis was most prominent in the midsecretory phase (peak progesterone), with disruption of the normal pattern of cycle-dependent DNA methylation changes, including a bias toward methylation of CpG islands, suggesting wide-range abnormalities of the chromatin remodeling machinery in endometriosis. DNA methylation changes were associated with altered gene expression relevant to endometrial function/dysfunction, including cell proliferation, inflammation/immune response, angiogenesis, and steroid hormone response. The data provide insight into epigenetic reprogramming and steroid hormone actions in endometrium contributing to the pathogenesis and pathophysiology of endometriosis.
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Houshdaran et al. found the greatest differences in methylation patterns between endometrium of endometriosis patients and control subjects in the midsecretory phase of the menstrual cycle.
“In accordance with numerous studies demonstrating progesterone resistance in the endometrium of patients in secretory phase, they also found the greatest differences in methylation patterns between the endometrium of patients and from control subjects in the midsecretory phase of menstrual cycle (100), further confirming molecular abnormalities apparent in eutopic endometrium of women with endomet”
From Biomarkers in endometriosis: Challenges and opportunities (2017) · cites this paper as [100]
Methylation patterns between endometriosis and control endometrium were not robust enough to be useful as diagnostic biomarkers independently from menstrual cycle.
“For example, despite finding significant methylation differences in CpG islands in the secretory phase of the menstrual cycle when endometrium samples are compared by disease (with or without endometriosis), the methylation patterns between disease and control were not simply robust to be useful as diagnostic biomarkers independently from menstrual cycle (82,100,104).”
From Biomarkers in endometriosis: Challenges and opportunities (2017) · cites this paper as [100]
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“in epigenetic marks such as DNA methylation and histone modifications.[23] Abnormal DNA methylation in EMS affects the expression of several genes, including homeobox A10, catechol‐O‐methyltransferase,[24] estrogen receptor beta (ERβ, ESR2), steroidogenic factor 1 (NR5A1), and aromatase (CYP19A1).”
Background
- Authors
- Houshdaran, S., Nezhat, C. R., Vo, K. C., Zelenko, Z., Irwin, J. C., & Giudice, L. C.
- Affiliations
- University of California, San Francisco (US)
- Center for Special Minimally Invasive and Robotic Surgery (US)
- Corresponding author
- Giudice, L. C.
- Venue
- Biology of Reproduction
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-08-17
- Volume
- 95
- Issue
- 5
- Pages
- 93-93
- ISSN
- 0006-3363 (ISSN-L)
- 1529-7268
- PMC
- PMC5178151
- OpenAlex
- W2513803129
- Cited by
- 113
- References
- 50
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 10 · 2023: 15 · 2022: 10 · 2021: 15 · 2020: 12 · 2019: 15 · 2018: 17 · 2017: 10
- FWCI
- 18.61
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc
- Locations
- Biology of Reproduction (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- BioOne Complete (BioOne) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD055764, P50HD055764)
- 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 › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Plant and fungal interactions
- Keywords
- endometriosis, methylome, gene expression, menstrual cycle, progesterone, CpG islands, chromatin remodeling, epigenetic reprogramming, steroid hormone response, inflammation, angiogenesis, cell proliferation, eutopic endometrium
- MeSH terms
- Adult, Endometriosis, Endometrium, Female, Gene Expression Regulation, Humans, Menstrual Cycle, Gene Expression, CpG Islands, DNA Methylation, Proteomics, Epigenesis, Genetic
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