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

作者：Vallve Juanico Julia; Suarez Salvador Elena; Castellvi Josep; Ballesteros Agustin; Taylor Hugh S; Gil Moreno Antonio; Santamaria Xavier^*

来源：Fertility and Sterility, 2017, 108(5): 858-+.

DOI：10.1016/j.fertnstert.2017.08.018

• Deep infiltrating endometriosis (DIE)
• epithelial mesenchymal transition (EMT)
• LGR5
• macrophages
• uterine aspirate

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.

• 出版日期2017-11