Endometriosis expresses a molecular pattern consistent with decreased retinoid uptake, metabolism and action

Mary Ellen Pavone*, Matthew Dyson, Scott Reirstad, Elizabeth Pearson, Hiroshi Ishikawa, You Hong Cheng, Serdar E. Bulun

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Background: Retinoic acid (RA) regulates key biological processes, including differentiation, apoptosis and cell survival. RA mediates induction of 17 beta-hydroxysteroid dehydrogenase type 2 mRNA, catalyzing the conversion of estradiol to estrone, in endometrium but not endometriosis because of a defect in endometriotic stromal cells. This defect may involve both the uptake and metabolism of RA. In this study, we analyze the expression of genes involved in RA signaling in normal endometrium and endometriosis. Methods: Tissue and stromal cells from ovarian endometriomas and eutopic endometrium from disease-free women were collected. Real-time reverse transcription-polymerase chain reaction was used to measure mRNA levels. Western blotting was used to evaluate protein expression. Results: We found that endometriotic tissue and stromal cells demonstrated significantly decreased mRNA expression of the major genes involved in RA signaling, including STRA6, CRBP1, ALDH1A2, CRABP2 and FABP5. We found increased levels of CYP26B1, responsible for RA metabolism. Nuclear extracts showed that RARα, RXRα and PPARβ/δ were underexpressed in both tissues and stromal cells from endometriotic tissue. Differences in protein levels were confirmed by western blotting. Conclusions: Endometriosis is characterized by a gene expression pattern suggesting a decrease in uptake and metabolism of RA. Because RA is integral in regulating key biological processes involved in cell survival, this alteration could partially explain the resistance to apoptosis found in endometriosis.

Original languageEnglish (US)
Pages (from-to)2157-2164
Number of pages8
JournalHuman Reproduction
Volume26
Issue number8
DOIs
StatePublished - Aug 2011

Keywords

  • apoptosis
  • endometriosis
  • endometrium
  • retinoic acid
  • retinoid

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology

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