title: Global Transcriptome Abnormalities of the Eutopic Endometrium From Women With Adenomyosis.
abstract: 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.
  
  
  
  Laboratory-based study with full institutional review board approval and consents.
  
  
  
  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.
  
  
  
  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.
  
  
  
  The eutopic endometrium in patients with adenomyosis has fundamental abnormalities that may predispose to invasion and survival beyond the myometrial interface.
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, CA, USA.
authors.forename: Christopher N
authors.initials: CN
authors.lastname: Herndon
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, CA, USA.
authors.forename: Lusine
authors.initials: L
authors.lastname: Aghajanova
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, CA, USA.
authors.forename: Shaina
authors.initials: S
authors.lastname: Balayan
authors.affiliation: Endocrine Technologies Support Core, Oregon National Primate Research Center, Beaverton, OR, USA.
authors.forename: David
authors.initials: D
authors.lastname: Erikson
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, CA, USA.
authors.forename: Fatima
authors.initials: F
authors.lastname: Barragan
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, CA, USA.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Goldfien
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, CA, USA.
authors.forename: Kim Chi
authors.initials: KC
authors.lastname: Vo
authors.affiliation: Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Shannon
authors.initials: S
authors.lastname: Hawkins
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, CA, USA linda.giudice@ucsf.edu.
authors.forename: Linda C
authors.initials: LC
authors.lastname: Giudice
mesh_terms: D062788:Adenomyosis / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D049109:Cell Proliferation; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D009215:Myometrium / Q000378:metabolism*; D059467:Transcriptome
keywords: adenomyosis; apoptosis; eutopic endometrium; microarray; signaling pathways