Global Transcriptome Abnormalities of the Eutopic Endometrium from Women with Adenomyosis
Open accessAbstract
Objective Adenomyosis is a clinical disorder defined by the presence of endometrial glands and stroma within the myometrium, the pathogenesis of which is poorly understood. We postulate that dysregulation of genes and pathways in eutopic endometrium may predispose to ectopic implantation. No study, to our knowledge, has examined the global transcriptome of isolated eutopic endometrium from women with clinically significant adenomyosis.Design Laboratory-based study with full institutional review board approval and consents.Material and methods Endometrial sampling was performed on hysterectomy specimens (proliferative phase) from symptomatic women with pathologically confirmed diffuse adenomyosis (n = 3). Controls (n = 5) were normo-ovulatory patients without adenomyosis. All patients were free from leiomyoma, endometriosis, and hormonal exposures. Isolated purified total RNA was subjected to microarray analysis using the Gene 1.0 ST Affymetrix platform. Data were analyzed with GeneSpring and Ingenuity Pathway analysis. Validation of several genes was undertaken by quantitative real-time reverse transcriptase polymerase chain reaction.Results Comparison of transcriptomes of proliferative endometrium from women with and without adenomyosis revealed 140 upregulated and 884 downregulated genes in samples from women with adenomyosis compared to controls. Highly differentially expressed genes include those involved in regulation of apoptosis, steroid hormone responsiveness, and proteins involved in extracellular matrix remodeling as well as microRNAs of unknown significance. Affected canonical pathways included eukaryotic initiation factor 2 signaling, oxidative phosphorylation, mitochondrial dysfunction, estrogen receptor signaling, and mammalian target of rapamycin signaling.Conclusion The eutopic endometrium in patients with adenomyosis has fundamental abnormalities that may predispose to invasion and survival beyond the myometrial interface.
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Normal endometrial stromal cells are very different in behavior from endometriotic or adenomyotic stromal cells.
“Yet normal endometrial stromal cells are very different in behavior from endometriotic or even adenomyotic stromal cells.”
From The Pathogenesis of Adenomyosis vis-à-vis Endometriosis (2020) · cites this paper as [65]
Over 1000 genes are differentially expressed between adenomyotic lesions and eutopic endometrium, and close to 1000 genes are differentially expressed between ectopic and eutopic endometrium.
“In fact, over 1000 genes are documented to be differentially expressed between adenomyotic lesions and eutopic endometrium [65] and close to 1000 genes are differentially expressed between ectopic and eutopic endometrium [66].”
From The Pathogenesis of Adenomyosis vis-à-vis Endometriosis (2020) · cites this paper as [65]
In the endometrium of women with endometriosis, several hundred minor biochemical changes have been described.
“In the endometrium of women with endometriosis several hundred minor biochemical changes have been described (124-128).”
From Pathogenesis of endometriosis: The genetic/epigenetic theory (2019) · cites this paper as [126]
More than 200 differences between the endometrium of women with and without endometriosis have been described.
“More than 200 differences between the endometrium of women with and without endometriosis were described (for recent reviews, see Refs.[169][170][171][172][173]).”
From Pathogenesis of deep endometriosis (2017) · cites this paper as [171]
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- Authors
- Herndon, C. N., Aghajanova, L., Balayan, S., Erikson, D., Barragan, F., Goldfien, G., Vo, K. C., Hawkins, S., & Giudice, L. C.
- Affiliations
- University of California, San Francisco (US)
- Oregon National Primate Research Center (US)
- Indiana University School of Medicine (US)
- Corresponding author
- Giudice, Linda C.
- ORCID
- Venue
- Reproductive Sciences
- Published
- 2016-10
- Volume
- 23
- Issue
- 10
- Pages
- 1289-1303
- ISSN
- 1933-7191 (ISSN-L)
- 1933-7205
- PMC
- PMC6344825
- OpenAlex
- W2396760331
- Cited by
- 106
- References
- 61
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 6 · 2023: 10 · 2022: 11 · 2021: 14 · 2020: 17 · 2019: 9 · 2018: 12 · 2017: 8 · 2016: 2
- FWCI
- 13.74
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Reproductive Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD007263)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Health Sciences › Medicine › Obstetrics and Gynecology › Uterine Myomas and Treatments
- Health Sciences › Medicine › Obstetrics and Gynecology › Gynecological conditions and treatments
- Keywords
- adenomyosis, eutopic endometrium, transcriptome, differentially expressed genes, endometrial gene expression, apoptosis regulation, extracellular matrix remodeling, EIF2 signaling, oxidative phosphorylation, mitochondrial dysfunction, estrogen receptor signaling, mTOR signaling, ectopic implantation, myometrial invasion
- MeSH terms
- Adult, Endometrium, Female, Humans, Myometrium, Gene Expression Profiling, Cell Proliferation, Transcriptome, Adenomyosis
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