The influence of menstrual cycle and endometriosis on endometrial methylome
Open accessAbstract
BACKGROUND: Alterations in endometrial DNA methylation profile have been proposed as one potential mechanism initiating the development of endometriosis. However, the normal endometrial methylome is influenced by the cyclic hormonal changes, and the menstrual cycle phase-dependent epigenetic signature should be considered when studying endometrial disorders. So far, no studies have been performed to evaluate the menstrual cycle influences and endometriosis-specific endometrial methylation pattern at the same time. RESULTS: Infinium HumanMethylation 450K BeadChip arrays were used to explore DNA methylation profiles of endometrial tissues from various menstrual cycle phases from 31 patients with endometriosis and 24 healthy women. The DNA methylation profile of patients and controls was highly similar and only 28 differentially methylated regions (DMRs) between patients and controls were found. However, the overall magnitude of the methylation differences between patients and controls was rather small (Δβ ranging from -0.01 to -0.16 and from 0.01 to 0.08, respectively, for hypo- and hypermethylated CpGs). Unsupervised hierarchical clustering of the methylation data divided endometrial samples based on the menstrual cycle phase rather than diseased/non-diseased status. Further analysis revealed a number of menstrual cycle phase-specific epigenetic changes with largest changes occurring during the late-secretory and menstrual phases when substantial rearrangements of endometrial tissue take place. Comparison of cycle phase- and endometriosis-specific methylation profile changes revealed that 13 out of 28 endometriosis-specific DMRs were present in both datasets. CONCLUSIONS: The results of our study accentuate the importance of considering normal cyclic epigenetic changes in studies investigating endometrium-related disease-specific methylation patterns.
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Endometrial biopsy by pipelle or curette is minimally invasive and can be useful to test endometrial receptivity in infertile women and as a diagnostic tool for endometriosis in an outpatient setting.
“The method of obtaining endometrial sample by either pipelle or curette is minimally invasive; however, aside from minimal discomfort for the patient, biopsy can prove to be a useful not only to test endometrial receptivity in infertile women with or without endometriosis (81), but also as a diagnostic tool for endometriosis in an outpatient setting (82).”
From Biomarkers in endometriosis: Challenges and opportunities (2017) · cites this paper as [82]
Saare et al. discourage the use of endometrial DNA methylome as biomarkers for endometriosis because significant methylation pattern differences in endometrium were not found that could discriminate patients from healthy women with acceptable sensitivity and specificity.
“Already, findings by Saare et al. discourage the use of endometrial DNA methylome as biomarkers for endometriosis, because significant methylation pattern differences in the endometrium were not found that could discriminate patients from healthy women with acceptable sensitivity and specificity (82).”
From Biomarkers in endometriosis: Challenges and opportunities (2017) · cites this paper as [82]
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 [82]
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- Authors
- Saare, M., Modhukur, V., Suhorutshenko, M., Rajashekar, B., Rekker, K., Sõritsa, D., Karro, H., Soplepmann, P., Sõritsa, A., Lindgren, C. M., Rahmioglu, N., Drong, A., Becker, C. M., Zondervan, K. T., Salumets, A., & Peters, M.
- Affiliations
- Tartu University Hospital (EE)
- University of Tartu (EE)
- Competence Centre on Health Technologies (Estonia) (EE)
- Centre for Human Genetics (GB)
- University of Oxford (GB)
- Corresponding author
- Saare, Merli
- ORCID
- Venue
- Clinical Epigenetics
- Published
- 2016-01-12
- Volume
- 8
- Issue
- 1
- Pages
- 2-2
- ISSN
- 1868-7075 (ISSN-L)
- 1868-7083
- PMC
- PMC4710036
- OpenAlex
- W2233824638
- Cited by
- 68
- References
- 45
- Citations by year
- 2025: 7 · 2024: 5 · 2023: 14 · 2022: 5 · 2021: 4 · 2020: 9 · 2019: 7 · 2018: 5 · 2017: 8 · 2016: 4
- FWCI
- 10.63
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Clinical Epigenetics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DSpace repository (University of Tartu) (submittedVersion, other-oa)
- Funders
- Estonian Ministry of Education and Research (IUT34-16)
- Ettevõtluse Arendamise Sihtasutus (EU48695)
- 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, endometrium, DNA methylation, menstrual cycle, epigenetics, differentially methylated regions, luteal phase, menstrual cycle phases, epigenetic biomarkers
- MeSH terms
- Adult, Endometriosis, Endometrium, Female, Humans, Menstrual Cycle, Case-Control Studies, DNA Methylation, Oligonucleotide Array Sequence Analysis, Epigenesis, Genetic, Genome-Wide Association Study
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