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BMC Medicine
Published in: BMC Medicine 1/2022

Open Access 01-12-2022 | Endometriosis | Research article

Single-cell analysis of menstrual endometrial tissues defines phenotypes associated with endometriosis

Authors: Andrew J. Shih, Robert P. Adelson, Himanshu Vashistha, Houman Khalili, Ashima Nayyar, Radha Puran, Rixsi Herrera, Prodyot K. Chatterjee, Annette T. Lee, Alexander M. Truskinovsky, Kristine Elmaliki, Margaret DeFranco, Christine N. Metz, Peter K. Gregersen

Published in: BMC Medicine | Issue 1/2022

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Abstract

Background

Endometriosis is a common, complex disorder which is underrecognized and subject to prolonged delays in diagnosis. It is accompanied by significant changes in the eutopic endometrial lining.

Methods

We have undertaken the first single-cell RNA-sequencing (scRNA-Seq) comparison of endometrial tissues in freshly collected menstrual effluent (ME) from 33 subjects, including confirmed endometriosis patients (cases) and controls as well as symptomatic subjects (who have chronic symptoms suggestive of endometriosis but have not been diagnosed).

Results

We identify a unique subcluster of proliferating uterine natural killer (uNK) cells in ME-tissues from controls that is almost absent from endometriosis cases, along with a striking reduction of total uNK cells in the ME of cases (p < 10−16). In addition, an IGFBP1+ decidualized subset of endometrial stromal cells are abundant in the shed endometrium of controls when compared to cases (p < 10−16) confirming findings of compromised decidualization of cultured stromal cells from cases. By contrast, endometrial stromal cells from cases are enriched in cells expressing pro-inflammatory and senescent phenotypes. An enrichment of B cells in the cases (p = 5.8 × 10−6) raises the possibility that some may have chronic endometritis, a disorder which predisposes to endometriosis.

Conclusions

We propose that characterization of endometrial tissues in ME will provide an effective screening tool for identifying endometriosis in patients with chronic symptoms suggestive of this disorder. This constitutes a major advance, since delayed diagnosis for many years is a major clinical problem in the evaluation of these patients. Comprehensive analysis of ME is expected to lead to new diagnostic and therapeutic approaches to endometriosis and other associated reproductive disorders such as female infertility.
Appendix
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Metadata
Title
Single-cell analysis of menstrual endometrial tissues defines phenotypes associated with endometriosis
Authors
Andrew J. Shih
Robert P. Adelson
Himanshu Vashistha
Houman Khalili
Ashima Nayyar
Radha Puran
Rixsi Herrera
Prodyot K. Chatterjee
Annette T. Lee
Alexander M. Truskinovsky
Kristine Elmaliki
Margaret DeFranco
Christine N. Metz
Peter K. Gregersen
Publication date
01-12-2022
Publisher
BioMed Central
Keyword
Endometriosis
Published in
BMC Medicine / Issue 1/2022
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-022-02500-3

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