Immune Cells Dominate Endometriosis Tissue in New Study
Publication Title: Redefining the contribution of retrograde menstruation to endometriosis: single-cell analysis of endometriotic lesions suggests a process more complex than simple autografting
Summary
- Question
- This study investigated the origins of cells within endometriotic lesions, a condition where uterine tissue grows outside the uterus, causing pain and infertility. Specifically, the researchers examined whether these lesions are primarily formed by endometrial cells from retrograde menstruation (backward flow of menstrual blood into the abdominal cavity) or by cells from the host's circulation.
- Why it Matters
- Endometriosis affects over 10% of reproductive-age women globally, leading to significant physical and emotional distress, as well as substantial healthcare costs. Current treatments focus on suppressing ovarian function or surgical removal of lesions, but these approaches often have limited effectiveness and high recurrence rates. Understanding the cellular makeup of endometriotic lesions can inform the development of new, more effective therapies targeting the disease's underlying mechanisms, potentially improving outcomes for millions of women.
- Methods
- The researchers used a mouse model of endometriosis by transplanting uterine tissue from genetically modified donor mice expressing green fluorescent protein (GFP) into wild-type recipient mice. This allowed them to distinguish donor-derived cells (GFP-positive) from host-derived cells (GFP-negative). After 18 weeks, they analyzed single-cell RNA sequencing data from the lesions to identify the types and origins of cells present.
- Key Findings
- The study found that 65% of the cells in endometriotic lesions were derived from the host's circulation, while only 35% originated from the transplanted uterine tissue. The host-derived cells included various immune cells, such as macrophages, T cells, B cells, and natural killer cells, as well as fibroblasts and endothelial cells. Key genes associated with endometriosis, including *KRAS*, *IGF-1*, and *MMP-2*, were highly expressed in these host-derived cells, suggesting their significant role in lesion development.
- Implications
- These findings challenge the traditional view that endometriosis is solely caused by retrograde menstruation and highlight the critical role of immune cells and other host-derived cells in lesion formation. This suggests that endometriosis is not just a hormonal disorder but also an immune-mediated condition. Targeting specific immune cells or cytokines may provide new therapeutic strategies beyond current hormonal treatments, potentially reducing recurrence rates and improving quality of life for patients.
- Next Steps
- The authors recommend further research to explore the functional roles of specific immune cell types and the signaling pathways involved in endometriotic lesion development. They also suggest investigating targeted immunotherapies as a potential treatment option for endometriosis.
- Funding Information
- This research was supported by the National Institutes of Health (award U54 HD052668). Additional funding was provided by the Endometriosis Foundation of America (grant AWD0003567). Yale University also provided funding and support for this research.
Full Citation
Mamillapalli R, Pyneni K, Watson K, Habata S, Gawde N, Taylor H. Redefining the contribution of retrograde menstruation to endometriosis: single-cell analysis of endometriotic lesions suggests a process more complex than simple autografting. Molecular Medicine 2026, 32: 41. PMID: 41714950, PMCID: PMC13020223, DOI: 10.1186/s10020-026-01442-3.
Authors
Ramanaiah Mamillapalli, PhD
First AuthorResearch Scientist
Hugh Taylor, MD
Last AuthorAnita O'Keeffe Young Professor of Obstetrics, Gynecology, and Reproductive Sciences and Professor of Molecular, Cellular, and Developmental Biology
Other Authors
Research Themes
Concepts
- endometriotic lesions;
- peritoneal implants;
- peritoneal cavity;
- natural killer (NK) cells;
- green fluorescent protein;
- development of endometriotic lesions;
- implantation of endometrium;
- wild type mice;
- development of endometriosis;
- single cell suspensions;
- infiltration of circulating cells;
- single-cell sequencing analysis;
- transplanted endometrium;
- uterine allograft;
- pelvic pain;
- donor mice;
- retrograde menstruation;
- T cells;
- uterine tissue;
- immune cells;
- type mice;
- B cells;
- gynecological disorders;
- endometriosis cells;
- single-cell analysis