Unique features of endometrial cells in endometriosis

Feb 20, 2025

New findings supportive of endometriosis to be an invasive disorder

Key Points

Highlights:

While most research on endometriosis has focused on its consequences, such as inflammation and fertility, less attention has been given to the causes of lesion formation.
Similar to metastasis, this likely involves enhanced migration, epithelial-to-mesenchymal transition, and intercellular interactions, including adhesion and gap junction formation that disrupt tissue barriers.

Importance:

Novel research could yield important clues on the role of endometrial cells in allowing endometriosis to be an invasive disorder.

What's done here:

Primary endometrial stromal (ESC) and epithelial cells(EEC) isolated from biopsies of women with and without endometriosis (n=22 for control and endometriosis groups).
Research methods included Cell culture, trans-mesothelial invasion assay, Gap junction intercellular coupling(GJIC) and blockade, motility assays, evaluation of cell to cell adhesion and mesothelial integrity by using appropriate techniques.

Main key features:

Endometrial stromal (ESCs) of endometriosis patients yield greater invasiveness across mesothelial monolayers than cells from healthy women, which is further enhanced by the presence of endometrial epithelial cells.
ESC and EEC mixtures from endometriosis patients exhibit increased invasiveness, with ESCs being the primary invasive cells.
ESCs from endometriosis patients demonstrate higher inherent motility.
Peritoneal mesothelial cells further enhance the motility of ESCs.
Peritoneal mesothelial cells induce gap junction intercellular coupling (GJIC) with ESCs.
GJIC is essential for the invasion of ESCs across the peritoneal mesothelium.

Lay Summary

Researchers from the University of Texas, San Antonio, have published a detailed study on the properties of endometrial cell components in relation to endometriosis, entitled "Hypersensitive intercellular responses of endometrial stromal cells drive invasion in endometriosis", in the scientific journal eLife.

The widely accepted theory of endometriosis suggests that during menstruation, endometrial cells enter the peritoneal cavity, leading to implantation and invasion similar to metastasis. However, limited research has focused on the cellular features of endometrial components that could facilitate this process.

The study involved isolating primary endometrial stromal and epithelial cells from biopsies of 22 women, both with and without endometriosis. The authors employed advanced molecular techniques, including cell culture, trans-mesothelial invasion assays, gap junction coupling blockade, Western blotting, immunohistochemistry, motility assays, homo- and hetero-cellular gap junction intercellular coupling assays, and atomic force microscopy for measuring cell-cell adhesion and mesothelial integrity.

The findings revealed that gap junction proteins were expressed at the cell surface when the endometrium interacted with the mesothelium, with endometrial stromal cells from endometriosis patients showing significantly higher expression than controls.

This research stands out for its use of diverse methodologies and its demonstration of gap junction coupling between endometrial stromal cells and the mesothelium. These novel insights support the role of endometrial cellular elements in the invasive nature of endometriosis.