Endometriosis expresses a molecular pattern consistent with decreased retinoid uptake, metabolism and action
Mary Ellen Pavone1, Matthew Dyson, Scott Reirstad
1Department of Obstetrics and Gynecology, Division of Reproductive Biology, Feinberg School of Medicine at Northwestern University, 303 Superior Street, Suite 4-123, Chicago, IL 60611, USA. mpavone@nmff.org
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.
Insights
Endometriosis shows altered retinoic acid (RA) signaling, with decreased gene expression for RA uptake and increased metabolism. This may explain reduced apoptosis in endometriosis patients.
Area of Science:
- Endocrinology and Reproductive Biology
- Molecular Biology
- Cell Biology
Background:
- Retinoic acid (RA) is crucial for cell differentiation, apoptosis, and survival.
- Endometriosis stromal cells exhibit a defect in RA signaling, affecting 17 beta-hydroxysteroid dehydrogenase type 2 mRNA induction.
- This defect may impair both RA uptake and metabolism in endometriosis.
Purpose of the Study:
- To investigate the expression of genes involved in retinoic acid (RA) signaling in normal endometrium versus endometriosis.
- To identify molecular mechanisms underlying altered RA signaling in endometriosis.
Main Methods:
- Collected tissue and stromal cells from ovarian endometriomas and eutopic endometrium.
- Utilized real-time reverse transcription-polymerase chain reaction (RT-PCR) for mRNA analysis.
- Employed Western blotting to assess protein expression levels.
Main Results:
- Significantly decreased mRNA expression of key RA signaling genes (STRA6, CRBP1, ALDH1A2, CRABP2, FABP5) in endometriosis.
- Increased expression of CYP26B1, an RA-metabolizing enzyme, in endometriosis.
- Underexpression of nuclear receptors RARα, RXRα, and PPARβ/δ in endometriotic tissues and cells, confirmed by Western blotting.
Conclusions:
- Endometriosis is characterized by impaired retinoic acid (RA) uptake and metabolism due to altered gene expression.
- This RA signaling dysregulation may contribute to the observed resistance to apoptosis in endometriosis.
- Findings suggest a potential role for RA pathway modulation in endometriosis treatment.
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