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.

OBJECTIVE

To characterize leucine-rich repeat containing G protein-coupled receptor 5-positive (LGR5) cells from the endometrium of women with endometriosis.

DESIGN

Prospective experimental study.

SETTING

University hospital/fertility clinic.

PATIENT(S): Twenty-seven women with endometriosis who underwent surgery and 12 healthy egg donors, together comprising 39 endometrial samples.

INTERVENTION(S): 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.

RESULT(S): 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.

CONCLUSION(S): 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.