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

Vallvé-Juanico, Júlia; Suárez-Salvador, Elena; Castellví, Josep; Ballesteros, A.; Taylor, Hugh S.; Costa, Xavier Santamaría

doi:10.1016/j.fertnstert.2017.08.018

Cited by 9 publications

(21 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Approximately half of the population of LGR5 + cells found in the endometrium co-express CD45, a leukocyte marker, and CD163, a monocyte and macrophage specific marker, suggesting a myeloid nature to the cells. This expression pattern was also observed by our group in LGR5 + cells from eutopic endometrium from women with endometriosis [8]. Interestingly, LGR5 + cells seem to remain constant throughout the menstrual cycle in normal human eutopic endometrium [7,9], although it was recently described that LGR5 expression decreases during the secretory phase [6].…”

Section: Introductionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 61%

“…Only four studies on LGR5 have been performed in healthy human eutopic endometrium and, to our knowledge, this is only the second work to explore LGR5 in the eutopic endometrium of women with endometriosis—the first study was published by our group [8]. Our previous work demonstrates an abnormal epithelial phenotype in the stromal compartment of eutopic endometrium of women with endometriosis [8], similar to what has been observed in mice with induced endometriosis [15]. LGR5 is aberrantly co-expressed with cytokeratin (CK) or E-cadherin (ECAD) in endometriotic eutopic endometrium, but this co-localization is not found in healthy women, suggesting that eutopic LCR5 + cells could have different behavior in endometriosis compared to healthy tissue [8].…”

Section: Discussionmentioning

confidence: 99%

“…Our previous work demonstrates an abnormal epithelial phenotype in the stromal compartment of eutopic endometrium of women with endometriosis [8], similar to what has been observed in mice with induced endometriosis [15]. LGR5 is aberrantly co-expressed with cytokeratin (CK) or E-cadherin (ECAD) in endometriotic eutopic endometrium, but this co-localization is not found in healthy women, suggesting that eutopic LCR5 + cells could have different behavior in endometriosis compared to healthy tissue [8]. Interestingly, we observed this process in both follicular and secretory phases of the menstrual cycle.…”

Section: Discussionmentioning

confidence: 99%

“…We previously described a special subset of LGR5 + cells that express unique genes in the eutopic endometrium of women with deep infiltrating endometriosis (DIE) compared to other types of endometriosis. These genes are related to immune system responses, hematological system development, and infertility [8]. Thus, we believe that LGR5 + cells could be implicated in aggressiveness and reproductive outcomes of the disease based on the function of these co-expressed genes.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Lgr5 Does Not Vary Throughout the Menstrual Cycle in Endometriotic Human Eutopic Endometrium

Vallvé-Juanico

Barón

Suárez-Salvador

et al. 2018

IJMS

Self Cite

View full text Add to dashboard Cite

Endometriosis is characterized by the abnormal presence of endometrium outside of the uterus, resulting in pelvic pain and infertility. The leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) has been postulated to be a marker of stem cells in the endometrium. However, LGR5+ cells have a macrophage-like phenotype in this tissue, so it is unclear what role LGR5+ cells actually play in the endometrium. Macrophages serve an important function in the endometrium to maintain fertility, while LGR5+ cells generally have a role in tumor progression and are involved in invasion in some cancers. We sought to determine whether LGR5+ cells vary across the menstrual cycle in women with endometriosis and whether there are implications for LGR5 in the aggressiveness of endometriosis and reproductive outcomes. We performed immunofluorescence, flow cytometry, and primary culture in vitro experiments on eutopic and ectopic endometrium from healthy and endometriosis patients and observed that neither LGR5+ cells nor LGR5 expression varied throughout the cycle. Interestingly, we observed that LGR5+ cell percentage overexpressing CD163 (anti-inflammatory marker) was higher in healthy endometrium, suggesting that in endometriosis, endometrium presents a more pro-inflammatory phenotype that likely leads to poor obstetric outcomes. We also observed higher levels of LGR5+ cells in ectopic lesions compared to eutopic endometrium and specifically in deep infiltrating endometriosis, indicating that LGR5 could be involved in progression and aggressiveness of the disease.

show abstract

Section: Introductionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Lgr5 Does Not Vary Throughout the Menstrual Cycle in Endometriotic Human Eutopic Endometrium

Vallvé-Juanico

Barón

Suárez-Salvador

et al. 2018

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

Macrophages display proinflammatory phenotypes in the eutopic endometrium of women with endometriosis with relevance to an infectious etiology of the disease

Vallvé-Juanico

Santamaría²,

et al. 2019

Fertility and Sterility

Self Cite

View full text Add to dashboard Cite

Objective: To phenotype transcriptomically M1 macrophages (Mf1) and M2 macrophages (Mf2) in the endometrium of women with endometriosis. Design: Prospective experimental study. Setting: University research laboratory. Patient(s): Six women with endometriosis and five controls without disease, in the secretory phase of the menstrual cycle. Intervention(s): Mf1, Mf2, uterine natural killer, and T regulatory cells were isolated from human endometrium using a uniquely designed cell-specific fluorescence activating cell sorting panel. Transcriptome profiles were assessed by RNA high sequencing, bioinformatics, and biological pathway analyses. Main Outcomes Measure(s): Differential gene expression between Mf1 and Mf2 in women with and without endometriosis and in Mf1 versus Mf2 in each group was determined and involved different biologic and signaling pathways. Result(s): Flow cytometry analysis showed no significant differences in total numbers of leukocytes between control and endometriosis groups, although Mf1 were higher in the endometriosis group versus controls. Statistical transcriptomic analysis was performed only in Mf1 and Mf2 populations due to larger sample sizes. Bioinformatic analyses revealed that in women with endometriosis, endometrial Mf1 are more proinflammatory than controls and that Mf2 paradoxically have a proinflammatory phenotype. Conclusion(s): As Mf are phenotypically plastic and their polarization state depends on their microenvironment, the altered endometrial environment in women with endometriosis may promote endometrial Mf2 polarization and an Mf1 proinflammatory phenotype. Moreover, aberrant phenotypes of Mf may contribute to abnormal gene expression of the eutopic endometrium and a proinflammatory environment in women with endometriosis relevant to the pathophysiology of the disease and compromised reproductive outcomes.

show abstract

Fibrinogen alpha chain is up-regulated and affects the pathogenesis of endometriosis

Chen

Cheng

et al. 2019

Reproductive BioMedicine Online

View full text Add to dashboard Cite

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

Cited by 9 publications

References 77 publications

Lgr5 Does Not Vary Throughout the Menstrual Cycle in Endometriotic Human Eutopic Endometrium

Lgr5 Does Not Vary Throughout the Menstrual Cycle in Endometriotic Human Eutopic Endometrium

Macrophages display proinflammatory phenotypes in the eutopic endometrium of women with endometriosis with relevance to an infectious etiology of the disease

Fibrinogen alpha chain is up-regulated and affects the pathogenesis of endometriosis

Contact Info

Product

Resources

About