Hypersensitive intercellular responses of endometrial stromal cells drive invasion in Endometriosis
- The University of Texas Health Science Center at San Antonio, United States
Abstract
Endometriosis is a debilitating disease affecting 190 million women worldwide and the greatest single contributor to infertility. The most broadly accepted etiology is that uterine endometrial cells retrogradely enter the peritoneum during menses, implant and form invasive lesions in a process analogous to cancer metastasis. However, over 90% of women suffer retrograde menstruation, but only 10% develop endometriosis, and debate continues as to whether the underlying defect is endometrial or peritoneal. Processes implicated in invasion include: enhanced motility; adhesion to, and formation of gap junctions with, the target tissue. Endometrial stromal (ESCs) from 22 endometriosis patients at different disease stages show much greater invasiveness across mesothelial (or endothelial) monolayers than ESCs from 22 control subjects, which is further enhanced by the presence of EECs. This is due to enhanced responsiveness of endometriosis ESCs to the mesothelium, which induces migration and gap junction coupling. ESC-PMC gap junction coupling is shown to be required for invasion, while coupling between PMCs enhances mesothelial barrier breakdown.
Data availability
As described in the MDAR, primary data results are reported as Supplementary Tables for all figures, except for Fig. 5, where data points are shown directly on the plots.Patient data is described, but samples are not available for extrenal use based on patient consent limitationsDNA sequences used for silencing studies are commercially available, and the source listed
Article and author information
Author details
Funding
Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD109027)
- Bruce J Nicholson
Cancer Prevention and Research Institute of Texas (RP160844)
- Bruce J Nicholson
National Center for Advancing Translational Sciences (UL1 TR 002645)
- Bruce J Nicholson
Cancer Prevention and Research Institute of Texas (RP150600.)
- Nameer B Kirma
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.NICHD supported the research project. CPRIT and NCATS supported key resources used extensively in the studies
Ethics
Human subjects: Explicit patient consent was obtained for all endometrial samples used in this study. All samples used in experiments were de-identified to the investigators. Approval for all protocols was obtained through the IRB at the Universoty of Texas Health San Antonio, IRB protocol # 20070728HR (8-31-23).
Copyright
© 2024, Chen et al.
This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
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Hypersensitive intercellular responses of endometrial stromal cells drive invasion in Endometriosis
eLife 13:e94778.
https://doi.org/10.7554/eLife.94778
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