Molecular Evidence for Differences in Endometrium in Severe Versus Mild Endometriosis
Open accessAbstract
Women with stage III/IV versus stage I/II endometriosis have lower implantation and pregnancy rates in natural and assisted reproduction cycles. To elucidate potential molecular mechanisms underlying these clinical observations, herein we investigated the transcriptome of eutopic endometrium across the menstrual cycle in the setting of severe versus mild endometriosis. Proliferative (PE), early secretory (ESE), and mid-secretory (MSE) endometrial tissues were obtained from 63 participants with endometriosis (19 mild and 44 severe). Purified RNA was subjected to microarray analysis using the Gene 1.0 ST Affymetrix platform. Data were analyzed with GeneSpring and Ingenuity Pathway Analysis and subsequently validated. Comparison of differentially regulated genes, analyzed by cycle phase, revealed dysregulation of progesterone and/or cyclic adenosine monophosphate (cAMP)-regulated genes and genes related to thyroid hormone action and metabolism. Also, members of the epidermal growth factor receptor (EGFR) signaling pathway were observed, with the greatest upregulation of EGFR in severe versus mild disease during the early secretory phase. The extracellular matrix proteoglycan versican (VCAN), which regulates cell proliferation and apoptosis, was the most highly expressed gene in severe versus mild disease. Upregulation of microRNA 21 (MIR21) and DICER1 transcripts suggests roles for microRNAs (miRNAs) in the pathogenesis of severe versus mild endometriosis, potentially through regulation of gene silencing and epigenetic mechanisms. These observed differences in transcriptomic signatures and signaling pathways may result in poorly programmed endometrium during the cycle, contributing to lower implantation and pregnancy rates in women with severe versus mild endometriosis.
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A microarray analysis of mild versus severe endometriosis confirmed a potential involvement of thyroid hormone homeostasis and metabolism in the pathophysiology of endometriosis.
“A microarray analysis of mild versus severe endometriosis confirmed a potential involvement of thyroid hormone homeostasis and metabolism in the pathophysiology of endometriosis [116].”
From Hormonal treatments for endometriosis: The endocrine background (2022) · cites this paper as [116]
This group further compared miRNA expression in women with mild and severe endometriosis and found increased endometrial expression of miR-21 and DICER in the more advanced stage of the disease.
“This group further compared miRNA expression in women with mild and severe endometriosis and found increased endometrial expression of miR-21 and DICER in the more advanced stage of the disease [126].”
From Update on biomarkers for the detection of endometriosis (2015) · cites this paper as [126]
Relatively few studies have compared miRNA expression in eutopic endometrium from women with and without surgically confirmed endometriosis.
“In contrast to studies comparing miRNA expression in eutopic versus ectopic endometrium, relatively few studies have compared miRNA expression in eutopic endometrium from women with and without surgically confirmed endometriosis [120, 125, 126].”
From Update on biomarkers for the detection of endometriosis (2015) · cites this paper as [126]
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- Authors
- Aghajanova, L., & Giudice, L. C.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Giudice, Linda C.
- Venue
- Reproductive Sciences
- Published
- 2011-03
- Volume
- 18
- Issue
- 3
- Pages
- 229-251
- ISSN
- 1933-7191 (ISSN-L)
- 1933-7205
- PMC
- PMC3118406
- OpenAlex
- W2146194938
- Cited by
- 146
- References
- 51
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 6 · 2023: 13 · 2022: 7 · 2021: 12 · 2020: 16 · 2019: 7 · 2018: 7 · 2017: 10 · 2016: 9 · 2015: 10 · 2014: 8 · 2013: 19 · 2012: 12
- FWCI
- 13.65
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Reproductive Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD055764)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Keywords
- endometriosis severity, eutopic endometrium, endometrial transcriptome, menstrual cycle, progesterone signaling, cAMP signaling, thyroid hormone metabolism, EGFR signaling, versican, extracellular matrix, miR-21, DICER1, implantation failure, miscarriage, endometrial receptivity
- MeSH terms
- Adult, Endometriosis, Endometrium, Female, Humans, Menstrual Cycle, RNA, Messenger, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Principal Component Analysis
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