Vitamin A interrupts epithelial-mesenchymal transition in endometriosis

Vitamin A inhibits EMT through IL-6 metabolism

Key Points

Highlights:

• The study highlighted the possible effect of vitamin A on endometriosis lesion formation and the mechanism underlying this effect.

Importance:

• The results of the study might open a perspective to produce drugs to treat endometriosis before the lesion formation occurs.

What's done here:

• Endometriotic samples were taken from the ovarian endometrioma of patients and control endometrial samples were obtained from the endometrium of patients without endometriosis (laparoscopically proven).
• Both endometrial stromal cells from the endometrium and endometriotic stromal cells from ovarian endometrioma have been purified and cultured.
• Vimentin, CD90, and CD146 staining have been applied to confirm endometriotic stem cell clusters.
• IL-6 levels from the culture medium before and after ATRA (retinoic acid) application have been measured.
• Also, the migration and invasion abilities of stromal cells have been measured before and after ATRA application and the alteration related to IL6 supplementation has been calculated.

Key Results:

• IL-6 has been shown to affect the EMT of endometriotic stromal cells.
• ATRA supplementation stopped migration and invasion of endometriotic cells, 
• The addition of IL6 on the ATRA supplemented cell plates negatively affected the process leading to an increase in migration ability of cells showing that ATRA inhibits EMT through decreasing IL-6 in endometriotic stem cells.

Limitations:

• The relatively small size of the study limits the suggestion potential of ATRA as an endometriosis drug so studies with larger sample sizes have to be done.

Lay Summary

The mechanism underlying the endometriosis formation is still not clear. Recent studies are focusing on the effect of retinoic acid and IL6 on epithelial-to-mesenchymal transition (EMT).

In the study conducted by Luyi Li et al, the researchers also questioned the relation between retinoic acid, IL-6, and EMT, in the paper published in "Annal of Palliative Medicine".

Endometriosis samples were taken from the ovarian endometrioma operations, and control endometrial samples were obtained from the eutopic endometrium of patients without endometriosis. The endometrial stromal cells from the eutopic endometrium and ovarian endometrioma have been purified and cultured to get stem cell clusters. immunohistochemical analysis by Vimentin, CD90, and CD146 was applied to confirm their stem cell nature. 

IL-6 levels from the culture medium before and after ATRA (retinoic acid) application have been measured. The migration and invasion capacities of stromal cells have also been measured before and after ATRA application, and the alteration related to IL6 supplementation has been calculated.

The results showed IL-6 has an effect on the EMT of endometriotic stromal stem cells. ATRA supplementation stopped the migration and invasion of endometriotic cells. The addition of IL6 on the ATRA supplemented cell plates negatively affected the process, leading to an increase in migration ability of cells showing that ATRA inhibits EMT through decreasing IL-6 in endometriotic stem cells.

The study turned on the torch through mesenchymal transformation and a possible role of retinoic acid to stop this. While the results should be confirmed on wider cohorts, it is still promising to have an opportunity like a vitamin supplementation on endometriosis treatment.

Research Source: https://pubmed.ncbi.nlm.nih.gov/34872261