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

Research output: Contribution to journalReview article

24 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1289-1303
Number of pages15
JournalReproductive Sciences
Volume23
Issue number10
DOIs
StatePublished - Oct 1 2016

    Fingerprint

Keywords

  • adenomyosis
  • apoptosis
  • eutopic endometrium
  • microarray
  • signaling pathways

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Herndon, C. N., Aghajanova, L., Balayan, S., Erikson, D., Barragan, F., Goldfien, G., Vo, K. C., Hawkins, S., & Giudice, L. C. (2016). Global Transcriptome Abnormalities of the Eutopic Endometrium from Women with Adenomyosis. Reproductive Sciences, 23(10), 1289-1303. https://doi.org/10.1177/1933719116650758