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

Fertil Steril. 2017 Nov;108(5):858-867.e2. doi: 10.1016/j.fertnstert.2017.08.018. Epub 2017 Sep 15.


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.

Keywords: Deep infiltrating endometriosis (DIE); LGR5; epithelial mesenchymal transition (EMT); macrophages; uterine aspirate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / analysis
  • Case-Control Studies
  • Endometriosis / genetics
  • Endometriosis / metabolism*
  • Endometriosis / pathology
  • Endometrium / chemistry*
  • Endometrium / pathology
  • Female
  • Fluorescent Antibody Technique
  • Gene Expression Profiling / methods
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Prospective Studies
  • Receptors, G-Protein-Coupled / analysis*
  • Receptors, G-Protein-Coupled / genetics
  • Sequence Analysis, RNA
  • Stromal Cells / chemistry*
  • Stromal Cells / pathology


  • Biomarkers
  • LGR5 protein, human
  • Receptors, G-Protein-Coupled