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

Mary Ellen Pavone, Matthew Dyson, Matthew T. Dyson, Reirstad S, S. Reirstad, Scott Reirstad, E. Pearson, Elizabeth Pearson, Pearson E, Hiroshi Ishikawa, Yu‐Chieh Cheng, Cheng YH, You Hong Cheng, Bulun Se, Serdar E. Bulun
Human Reproduction · 2011 · vol. 26(8) , pp. 2157–2164 · doi:10.1093/humrep/der172 · PMID:21659316 · PMC3137392 · W2113098130
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Endometriosis tissue exhibits decreased expression of genes involved in retinoid uptake and action, alongside increased expression of retinoid-metabolizing enzymes, suggesting impaired retinoid signaling.

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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.

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Condition tags

endometriosis

MeSH descriptors

Cytochrome P-450 Enzyme System Endometriosis Endometrium Membrane Proteins Retinal Dehydrogenase Retinol-Binding Proteins, Cellular Stromal Cells Tretinoin Adult Adult Aldehyde Dehydrogenase 1 Family Aldehyde Dehydrogenase 1 Family Cytochrome P-450 Enzyme System Cytochrome P-450 Enzyme System Endometriosis Endometriosis Endometriosis Endometrium Endometrium Fatty Acid-Binding Proteins

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