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Reproductive Sciences

, Volume 19, Issue 2, pp 152–162 | Cite as

Nuclear Receptor, Coregulator Signaling, and Chromatin Remodeling Pathways Suggest Involvement of the Epigenome in the Steroid Hormone Response of Endometrium and Abnormalities in Endometriosis

  • Z. Zelenko
  • L. Aghajanova
  • J. C. Irwin
  • Linda C. GiudiceEmail author
Original Articles

Abstract

Human endometrium, a steroid hormone-dependent tissue, displays complex cellular regulation mediated by nuclear receptors (NRs). The NRs interact with histone-modifying and DNA-methylating/-demethylating enzymes in the transcriptional complex. We investigated NRs, their coregulators, and associated signaling pathways in endometrium across the normal menstrual cycle and in endometriosis, an estrogen-dependent, progesterone-resistant disorder. Endometrial tissue was processed for analysis of 84 genes using NR and coregulator polymerase chain reaction (PCR) arrays. Select genes were validated by immunohistochemistry. Ingenuity pathway analysis identified DNA methylation and transcriptional repression signaling as the most affected pathway in endometrium in women with versus without endometriosis, regardless of cycle phase. Thyroid hormone receptor (THR) and vitamin D receptor (VDR) pathways were also regulated in normal and disease endometrium by activation of TH or vitamin D regulated genes. These data support the involvement of the epigenome in steroid hormone response of normal endometrium throughout the cycle and abnormalities in endometrium in women with endometriosis.

Keywords

endometriosis nuclear receptors coregulators DNA methylation histone deacetylases 

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Copyright information

© Society for Reproductive Investigation 2012

Authors and Affiliations

  • Z. Zelenko
    • 1
  • L. Aghajanova
    • 1
  • J. C. Irwin
    • 1
  • Linda C. Giudice
    • 1
    Email author
  1. 1.Department of Obstetrics, Gynecology and Reproductive SciencesUniversity of CaliforniaSan FranciscoUSA

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