Aberrant expression of epithelial leucine-rich repeat containing G protein–coupled receptor 5–positive cells in the eutopic endometrium in endometriosis and implications in deep-infiltrating endometriosis
We identified aberrantly located leucine-rich repeat containing G protein-coupled receptor 5-positive cells coexpressing epithelial markers in the stromal compartment of endometriotic endometrium that have a different expression profile in deep-infiltrating endometriosis.
Volume 108, Issue 5, Pages 858–867.e2
Júlia Vallvé-Juanico, M.S., Elena Suárez-Salvador, M.D., Josep Castellví, M.D., Ph.D., Agustín Ballesteros, M.D., Ph.D., Hugh S. Taylor, M.D., Antonio Gil-Moreno, M.D., Ph.D., Xavier Santamaria, M.D., Ph.D.
To characterize leucine-rich repeat containing G protein-coupled receptor 5–positive (LGR5+) cells from the endometrium of women with endometriosis.
Prospective experimental study.
University hospital/fertility clinic.
Twenty-seven women with endometriosis who underwent surgery and 12 healthy egg donors, together comprising 39 endometrial samples.
Obtaining of uterine aspirates by using a Cornier Pipelle.
Main Outcomes Measure(s)
Immunofluorescence in formalin-fixed paraffin-embedded tissue from mice and healthy and pathologic human endometrium using antibodies against LGR5, E-cadherin, and cytokeratin, and epithelial and stromal LGR5+ cells isolated from healthy and pathologic human eutopic endometrium by fluorescence-activated cell sorting and transcriptomic characterization by RNA high sequencing.
Immunofluorescence showed that LGR5+ cells colocalized with epithelial markers in the stroma of the endometrium only in endometriotic patients. The results from RNA high sequencing of LGR5+ cells from epithelium and stroma did not show any statistically significant differences between them. The LGR5+ versus LGR5− cells in pathologic endometrium showed 394 differentially expressed genes. The LGR5+ cells in deep-infiltrating endometriosis expressed inflammatory markers not present in the other types of the disease.
Our results revealed the presence of aberrantly located LGR5+ cells coexpressing epithelial markers in the stromal compartment of women with endometriosis. These cells have a statistically significantly different expression profile in deep-infiltrating endometriosis in comparison with other types of endometriosis, independent of the menstrual cycle phase. Further studies are needed to elucidate their role and influence in reproductive outcomes.