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Updated: Sep 28, 2025

Mouse Model of Surgically-induced Endometriosis by Auto-transplantation of Uterine Tissue
Published on: January 6, 2012
Resveratrol impairs cellular mechanisms associated with the pathogenesis of endometriosis
Daniela Madanes1, Gabriela Meresman2, Sofía A Valla3
1Immunology of the Reproduction Laboratory, Ibyme-Conicet, Buenos Aires C1428ADN, Argentina.
Research Question:
Does resveratrol exert a potent inhibitory effect on the development of endometriosis by interfering with some pivotal processes?
Design:
In-vitro cultures of primary endometriotic stromal cells, immortalized endometrial stromal (St-T1b) and endometriotic epithelial (12Z) cells were used to assess the effects of resveratrol on endometrial cell mechanisms. The effects of resveratrol on 12Z and St-T1b cell viability were assessed by MTT assay, apoptosis by FITC Annexin V assay and cleaved caspase-3 levels and cell migration by wound healing assay. The effect of resveratrol on the expression of genes related to cell migration, angiogenesis and cell stemness was evaluated by qRT-PCR.
Results:
Resveratrol significantly decreased cell viability (P= 0.0065 to P = 0.0180), cell migration (P < 0.001 to P = 0.0225) and increased the number of apoptotic cells (P = 0.0031 to P = 0.0432) in both cell lines. In cell lines and primary culture, the treatment reduced MMP-2/TIMP-1 (P < 0.001 to P = 0.0180), VEGF (P = 0.0052 to P = 0.0243) and Ang-1 mRNA (P < 0.001 to P = 0.0382) expression. Among the stem cell phenotype markers, resveratrol 100 µM increased mRNA expression levels of Notch-1 (P < 0.001 to P = 0.0018), KLF-4 (P = 0.0011 to P = 0.0137), SOX-2 (P < 0.001 to P = 0.0070) and TERT (P < 0.001 to P = 0.0193) in both cell lines and primary cultures. The mRNA expression level of Snail-1 increased in the cell lines (P < 0.001 to P = 0.0087), whereas OCT-4 mRNA expression increased in St-T1b (P = 0.0396) and primary cultures (P = 0.0148). Vimentin mRNA expression showed a significant upregulation in primary cultures (P < 0.001). The expression of Msi-1 (P = 0.0145) and NANOG (P = 0.0080) decreased only in St-T1b cells.
Conclusion:
Resveratrol showed inhibitory effects on cell behaviour related to the development of endometriosis by differentially affecting growth, apoptosis, migration and stem cell phenotype of endometrial and endometriotic cells in vitro.
Insights
Resveratrol inhibits endometriosis development by reducing cell viability and migration while promoting apoptosis in endometrial cells. It also modulates gene expression related to angiogenesis and stemness, suggesting a multifaceted therapeutic potential.
Area of Science:
- Gynecology
- Cell Biology
- Pharmacology
Background:
- Endometriosis is a chronic, estrogen-dependent inflammatory disease.
- Current treatments for endometriosis have limitations and side effects.
- Resveratrol, a natural polyphenol, has demonstrated anti-inflammatory and anti-cancer properties.
Purpose of the Study:
- To investigate the inhibitory effects of resveratrol on endometriosis development in vitro.
- To explore the mechanisms by which resveratrol affects endometriotic and endometrial cells.
Main Methods:
- In vitro cultures of primary endometriotic stromal cells, immortalized endometrial stromal (St-T1b), and endometriotic epithelial (12Z) cells were used.
- Cell viability, apoptosis, and migration were assessed using MTT assay, FITC Annexin V assay, and wound healing assay, respectively.
- Gene expression related to cell migration, angiogenesis, and stemness was evaluated by quantitative real-time PCR (qRT-PCR).
Main Results:
- Resveratrol significantly decreased cell viability and migration while increasing apoptosis in both cell lines.
- Resveratrol treatment reduced the expression of genes involved in angiogenesis, including MMP-2/TIMP-1, VEGF, and Ang-1.
- Resveratrol modulated stem cell phenotype markers, increasing Notch-1, KLF-4, SOX-2, and TERT, while affecting Snail-1, OCT-4, Vimentin, Msi-1, and NANOG expression differentially.
Conclusions:
- Resveratrol exhibits potent inhibitory effects on cell behavior crucial for endometriosis development.
- The compound differentially affects growth, apoptosis, migration, and stem cell phenotype of endometrial and endometriotic cells in vitro.
- Resveratrol holds potential as a therapeutic agent for endometriosis.
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