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Updated: Nov 26, 2025
Author Spotlight: Advancing Reproductive Immunology with a Protocol for the Quantitative Evaluation of Endometrial Immune Cells
Published on: October 13, 2023
Comprehensive analysis utilizing flow cytometry and immunohistochemistry reveals inflammatory changes in local
A J Hey-Cunningham1, C Wong1, J Hsu2
1The University of Sydney Obstetrics, Gynaecology and Neonatology, Central Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
Insights
Endometriosis alters dendritic cell (DC) populations in both the endometrium and circulation. These immune cell changes, particularly myeloid DCs (mDCs), are linked to disease stage and suggest a persistently inflammatory environment.
Area of Science:
- Reproductive immunology
- Cellular immunology
- Gynecologic pathology
Background:
- Immune dysregulation is implicated in endometriosis pathogenesis and infertility.
- Endometrial dendritic cell (DC) alterations in endometriosis are suspected but not fully characterized.
- Comprehensive investigation of DC subsets in both endometrium and peripheral blood is lacking.
Purpose of the Study:
- To detail endometrial and systemic dendritic cell (DC) subset disturbances in women with endometriosis.
- To investigate the relationship between DC populations, endometriosis disease stage, and menstrual cycle phase.
- To explore the implications of these DC alterations for the inflammatory environment in endometriosis.
Main Methods:
- A prospective, cross-sectional cohort study involving 55 women with endometriosis and 30 controls.
- Analysis of circulating and endometrial dendritic cell (DC) populations using flow cytometry and immunohistochemistry.
- Correlation of DC subset proportions with American Society for Reproductive Medicine (ASRM) endometriosis stage and menstrual cycle phase.
Main Results:
- Endometrial myeloid DCs (mDCs) and plasmacytoid DCs were identified.
- Increased IRF-8+ cells and total DCs were observed in the endometrium of women with endometriosis, with blunted cyclical fluctuations.
- Advanced endometriosis stages correlated with specific inflammatory DC changes in the endometrium and increased circulating CD141+ mDCs.
Conclusions:
- Endometriosis is associated with distinct endometrial and systemic dendritic cell (DC) subset disturbances.
- These DC alterations indicate a chronic inflammatory state within the endometrium, particularly in advanced disease.
- Further characterization of immune cell subtypes is crucial for understanding endometriosis and its associated infertility.
Study Question:
What are the detailed endometrial tissue specific and systemic dendritic cell (DC) subset disturbances in endometriosis?
Summary Answer:
This study confirms myeloid DC (mDC) and plasmacytoid DC subsets are readily identified in endometrial tissue and shows both endometrial and circulating differences in DC populations in women with endometriosis, with disease stage-specific relationships evident locally in the endometrium.
What Is Known Already:
Immune factors in the uterus, the peritoneal environment and systemically are implicated in the pathogenesis and progression of both endometriosis and infertility. While there is some evidence that endometrial DC populations are altered in endometriosis, DC subset involvement in both the endometrium and peripheral blood have not been comprehensively investigated so the functional consequences have been unknown.
Study Design, Size, Duration:
This prospective cross-sectional cohort study compares circulating and endometrial DC populations in women of reproductive age with and without endometriosis (n = 55 and 30, respectively), wherein each participant donated samples at a single time point. Study participants were surveyed for menstrual cycle phase, American Society for Reproductive Medicine (ASRM) endometriosis disease stage and fertility status (where possible).
Participants/Materials, Setting, Methods:
Peripheral blood samples were processed into mononuclear cells for analysis by flow cytometry, and endometrial samples were analysed by immunohistochemistry and dissociated into single-cell suspension for flow cytometry.
Main Results And The Role Of Chance:
In the endometrium of women with endometriosis, IRF-8+ cells were increased during the proliferative phase (P = 0.014), total DC proportions increased in the secretory phase (P = 0.038) and normal menstrual cyclical fluctuations in CD1c+ and IRF-8+ cells blunted; indicative of a consistently inflammatory tissue environment. The inflammatory changes in CD141+ and IRF-8+ populations in the endometrium of women with endometriosis were particularly evident in more advanced ASRM stages of the disease (respective P-values 0.032 and 0.045). There was also evidence of systemic inflammation in women with endometriosis, with increased circulating CD141+ mDC proportions (overall P = 0.040, secretory phase P = 0.021).
Large Scale Data:
N/A.
Limitations, Reasons For Caution:
As is common in this type of study, one of the main limitations was small sample numbers, particularly during the menstrual phase of the cycle.
Wider Implications Of The Findings:
Further phenotyping of local and circulating immune cell subtypes is critical to improving understanding of endometriosis pathogenesis and immune contributions to infertility associated with the disease.
Study Funding/Competing Interest(S):
This research was financially supported by a Sydney Medical School and Balnaves Foundation Kick Start Grant and the Department of Obstetrics, Gynaecology and Neonatology at The University of Sydney. The authors have no conflicts of interest to declare.
