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A Syngeneic Murine Model of Endometriosis using Naturally Cycling Mice
Published on: November 24, 2020
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Endometriosis and nuclear receptors
Bahar D Yilmaz1, Serdar E Bulun1
1Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, 250 E. Superior Street, Chicago, IL, USA.
Human Reproduction Update
|February 28, 2019
Summary
Nuclear receptors (NRs) play a key role in endometriosis, a steroid-dependent disorder. Understanding NR functions in estrogen biosynthesis, inflammation, and progesterone resistance may lead to new treatments for endometriosis.
Area of Science:
- Reproductive biology
- Endocrinology
- Molecular biology
Background:
- Endometriosis is a complex steroid-dependent disorder.
- The precise roles of nuclear receptors (NRs) in endometriosis pathophysiology are not fully understood.
- Recent breakthroughs highlight NR involvement in key disease mechanisms.
Purpose of the Study:
- To review and clarify new information on NR mechanisms in endometriosis.
- To emphasize the roles of specific NRs in excessive estrogen biosynthesis, inflammation, progesterone resistance, and survival.
- To explore potential therapeutic targets based on NR dysregulation.
Main Methods:
- Comprehensive literature search of PubMed (human, animal, cellular studies until 2018).
- Focused on endometriosis, steroid/orphan NRs (ESR1, ESR2, PGR, NR5A1, NR2F2), and retinoids.
- Analysis of NR expression and function in endometriotic tissues.
Main Results:
- Endometriotic stromal cells exhibit dysregulated differentiation, epigenetic abnormalities, and altered NR expression.
- NR5A1 dominance drives excessive estrogen production, while high ESR2 promotes estrogen-driven inflammation.
- Deficiency in progesterone receptor (PGR) leads to progesterone resistance and impaired retinoid synthesis.
Conclusions:
- Abnormal NR expression and function contribute to endometriosis progression, inflammation, and cell survival.
- NR-related abnormalities interact with epigenetic defects, exacerbating disease.
- Targeting NRs (PGR, retinoic acid receptors, ESR2) offers potential novel therapeutic strategies for endometriosis.
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