Global Transcriptome Abnormalities of the Eutopic Endometrium From Women With Adenomyosis

Christopher N Herndon; Lusine Aghajanova; Shaina Balayan; David Erikson; Fatima Barragan; Gabriel Goldfien; Kim Chi Vo; Shannon Hawkins; Linda C Giudice

doi:10.1177/1933719116650758

Global Transcriptome Abnormalities of the Eutopic Endometrium From Women With Adenomyosis

Reprod Sci. 2016 Oct;23(10):1289-303. doi: 10.1177/1933719116650758. Epub 2016 May 27.

Authors

Christopher N Herndon¹, Lusine Aghajanova¹, Shaina Balayan¹, David Erikson², Fatima Barragan¹, Gabriel Goldfien¹, Kim Chi Vo¹, Shannon Hawkins³, Linda C Giudice⁴

Affiliations

¹ Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, CA, USA.
² Endocrine Technologies Support Core, Oregon National Primate Research Center, Beaverton, OR, USA.
³ Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, IN, USA.
⁴ Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, CA, USA linda.giudice@ucsf.edu.

Abstract

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.

Keywords: adenomyosis; apoptosis; eutopic endometrium; microarray; signaling pathways.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Adenomyosis / genetics*
Adenomyosis / metabolism
Adult
Cell Proliferation
Endometrium / metabolism*
Female
Gene Expression Profiling
Humans
Myometrium / metabolism*
Transcriptome*

Grants and funding

T32 HD007263/HD/NICHD NIH HHS/United States