Abstract
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.
Graphical Abstract
Graphical Abstract
KEYWORDS
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Biography
Daniela Madanes is a PhD student at the Institute of Experimental Biology and Medicine from National Research Council, Argentina. She is interested in understanding the dynamic nature of the eutopic and ectopic endometrium in endometriosis to find novel therapeutic strategies in accordance with the needs of the patient.
Key message
Resveratrol exerts inhibitory effects on some pivotal processes involved in endometriosis development. Understanding the basic mechanism of action of this polyphenol is key to determining its potential benefits for patients suffering from endometriosis and for it to be considered as a novel therapeutic strategy.
Article info
Publication history
Published online: February 15, 2022
Accepted:
February 9,
2022
Received in revised form:
January 11,
2022
Received:
October 18,
2021
Footnotes
Declaration: The authors report no financial or commercial conflicts of interest.
Identification
Copyright
Published by Elsevier Ltd on behalf of Reproductive Healthcare Ltd.
