Macrophage Plasticity and Extracellular Vesicles in Endometriosis: Immunopathology and Therapeutic Perspectives

Saba Safdarpour; Parisa Nadri; Nima Azari‐Dolatabad

doi:10.1007/s43032-025-01896-6

Macrophage Plasticity and Extracellular Vesicles in Endometriosis: Immunopathology and Therapeutic Perspectives

Saba Safdarpour, Parisa Nadri, Nima Azari‐Dolatabad

Reproductive sciences (Thousand Oaks, Calif.) · 2025 · vol. 32(7) , pp. 2065–2079 · doi:10.1007/s43032-025-01896-6 · PMID:40481352 · W4411089889

review OA: closed CC0 ⤵ 1 in-corpus citation

Limited metadata. Only one source feed has indexed this record so far — no abstract, full text, or open-access copy is available through Endo Lab. The publisher's page (linked below) is the canonical location for the actual content. If you have institutional access, use "Find at my library".

View at publisher → View on OpenAlex View on PubMed

⚙ AI-generated summary by claude@2026-06+body, 2026-06-07 ⓘ

This review examines macrophage polarization and extracellular vesicle involvement in endometriosis immunopathology, discussing their therapeutic potential.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

⚙ AI-generated deep summary by claude@2026-06, 2026-06-07 ⓘ

This paper is a narrative review examining how macrophage polarization and macrophage-derived extracellular vesicles (EVs) contribute to endometriosis immunopathology and possible immunomodulatory therapeutic strategies. It describes that endometriotic lesions contain M2-like macrophages associated with tissue reconstruction, angiogenesis, and immune evasion, and that lesion persistence along with neurogenesis and inflammation are linked to macrophage-derived EVs, cytokines, and growth factors. A key limitation explicitly stated is that the article generates no new data and is based on previously published information rather than original experiments. This paper is centrally about endometriosis — it focuses on macrophage plasticity and extracellular vesicles as mechanisms driving endometriosis and as therapeutic targets.

Read from the paper's body, not the abstract. Not a substitute for reading the paper. No clinical advice. How this works

My notes (saved in your browser only)

Condition tags

endometriosis

MeSH descriptors

Cell Plasticity Cell Plasticity Cell Plasticity Cell Plasticity Cell Plasticity Cell Plasticity Cell Plasticity Cell Plasticity Cell Plasticity Cell Plasticity Cell Plasticity Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (93)

Altered Immunity in Endometriosis: What Came First? via openalex
Alternative activation of macrophages in rhesus macaques (Macaca mulatta) with endometriosis. via openalex
Assessing research gaps and unmet needs in endometriosis via openalex
Correction to: Endometriosis and Adenomyosis: Global Perspectives Across the Lifespan via openalex
Deficiency of MST1 in endometriosis related peritoneal macrophages promoted the autophagy of ectopic endometrial stromal cells by IL-10 via openalex
Discovery of Phosphatidic Acid, Phosphatidylcholine, and Phosphatidylserine as Biomarkers for Early Diagnosis of Endometriosis via openalex
Endometrial stromal cells treated by tumor necrosis factor‐α stimulate macrophages polarized toward M2 via interleukin‐6 and monocyte chemoattractant protein‐1 via openalex
Endometriosis, a disease of the macrophage via openalex
Endometriosis and Cancer: Exploring the Role of Macrophages via openalex
Endometriosis-Associated Macrophages: Origin, Phenotype, and Function via openalex
Endometriosis: epidemiology and aetiological factors via openalex
Endometriosis Misdiagnosis via openalex
Endometriosis Patients Show an Increased M2 Response in the Peritoneal CD14+low/CD68+low Macrophage Subpopulation Coupled with an Increase in the T-helper 2 and T-regulatory Cells via openalex
Endometriosis through an immunological lens: a pathophysiology based in immune dysregulation via openalex
Estrogen receptor β upregulates CCL2 via NF-κB signaling in endometriotic stromal cells and recruits macrophages to promote the pathogenesis of endometriosis via openalex
Evaluation of M1 and M2 macrophages in ovarian endometriomas from women affected by endometriosis at different stages of the disease via openalex
Expression of MMIF, HIF-1α and VEGF in Serum and Endometrial Tissues of Patients with Endometriosis via openalex
Extracellular vesicles in endometrial-related diseases: role, potential and challenges via openalex
Extracellular vesicles in endometriosis: role and potential via openalex
Future Directions in Endometriosis Research and Therapeutics via openalex
Future of Endometriosis Research via openalex
G-CSF and IL-6 may be involved in formation of endometriosis lesions by increasing the expression of angiogenic factors in neutrophils via openalex
Higher expression of vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 (Flk-1) and metalloproteinase-9 (MMP-9) in a rat model of peritoneal endometriosis is similar to cancer diseases via openalex
Immunosuppressive Extracellular Vesicles as a Linking Factor in the Development of Tumor and Endometriotic Lesions in the Gynecologic Tract via openalex
Inflammatory Mediators and Pain in Endometriosis: A Systematic Review via openalex
Interleukin-33 modulates inflammation in endometriosis via openalex
Intra-uterine microbial colonization and occurrence of endometritis in women with endometriosis† via openalex
Involvement of the nuclear factor-κB pathway in the pathogenesis of endometriosis via openalex
M1 Macrophage-Derived Nanovesicles Repolarize M2 Macrophages for Inhibiting the Development of Endometriosis via openalex
Macrophages Are Alternatively Activated in Patients with Endometriosis and Required for Growth and Vascularization of Lesions in a Mouse Model of Disease via openalex
Macrophages inhibit and enhance endometriosis depending on their origin via openalex
MCP-1 exerts the inflammatory response via ILK activation during endometriosis pathogenesis via openalex
Nuclear Factor-κB (NF-κB): An Unsuspected Major Culprit in the Pathogenesis of Endometriosis That Is Still at Large? via openalex
Pathogenesis of Endometriosis: Role of Macrophages in Endometriosis via openalex
Pelvic pain correlates with peritoneal macrophage abundance not endometriosis via openalex
Rediscovering peritoneal macrophages in a murine endometriosis model via openalex
Regulation of Inflammation Pathways and Inflammasome by Sex Steroid Hormones in Endometriosis via openalex
Role of cytokines in endometriosis via openalex
Roles of microRNAs in Regulating Apoptosis in the Pathogenesis of Endometriosis via openalex
Serum and Ectopic Endometrium from Women with Endometriosis Modulate Macrophage M1/M2 Polarization via the Smad2/Smad3 Pathway via openalex
Targeting delivery of mifepristone to endometrial dysfunctional macrophages for endometriosis therapy via openalex
The Delicate Balance between the Good and the Bad IL-1 Proinflammatory Effects in Endometriosis via openalex
The effects of resveratrol on the expression of VEGF, TGF-β, and MMP-9 in endometrial stromal cells of women with endometriosis via openalex
The Essential Role of GATA6 in the Activation of Estrogen Synthesis in Endometriosis via openalex
The Extracellular Vesicle–Macrophage Regulatory Axis: A Novel Pathogenesis for Endometriosis via openalex
The Known, the Unknown and the Future of the Pathophysiology of Endometriosis via openalex
The Role of Cytokines in Endometriosis* via openalex
The Role of Peritoneal Macrophages in Endometriosis via openalex
The role of small extracellular vesicle-miRNAs in endometriosis via openalex
The role of TGF-β in the pathophysiology of peritoneal endometriosis via openalex
Tumor necrosis factor alpha secretion by peritoneal macrophages in patients with endometriosis via openalex
Understanding endometriosis from an immunomicroenvironmental perspective via openalex
Unraveling pathogenesis, biomarkers and potential therapeutic agents for endometriosis associated with disulfidptosis based on bioinformatics analysis, machine learning and experiment validation via openalex
VEGF Receptor 1-Expressing Macrophages Recruited from Bone Marrow Enhances Angiogenesis in Endometrial Tissues via openalex
World Endometriosis Society consensus on the classification of endometriosis via openalex
W6809509812 via openalex
W1996123579 via openalex
W2055348159 via openalex
W2099944775 via openalex
W2101278668 via openalex
W2140246703 via openalex
W2164385268 via openalex
W2231237922 via openalex
W2398274827 via openalex
W2596152408 via openalex
W2605484523 via openalex
W2914782620 via openalex
W2945953423 via openalex
W2999016253 via openalex
W3008724147 via openalex
W3013522609 via openalex
W3115000310 via openalex
W3136714565 via openalex
W3185900610 via openalex
W3208517554 via openalex
W4214754424 via openalex
W4225871809 via openalex
W4385475981 via openalex
W4386542331 via openalex
W4386987394 via openalex
W4387306878 via openalex
W4387427325 via openalex
W4388406732 via openalex
W4388692094 via openalex
W4391812948 via openalex
W4400585127 via openalex
W4401383189 via openalex
W4401574886 via openalex
W4402607849 via openalex
W4403922472 via openalex
W4406020920 via openalex
W4406334387 via openalex
W1970087698 via openalex

Cited by (1)

Associations between aggregate index of systemic inflammation and endometriosis risk utilizing logistic regression analysis 2026

Source provenance

europepmc: last seen: 2026-06-04T01:30:01.192114+00:00
openalex: last seen: 2026-06-10T17:14:06.276822+00:00
pubmed: last seen: 2026-05-18T00:31:18.686456+00:00

License: CC0 · commercial use OK

[1] Altered Immunity in Endometriosis: What Came First? via openalex

[2] Alternative activation of macrophages in rhesus macaques (Macaca mulatta) with endometriosis. via openalex

[3] Assessing research gaps and unmet needs in endometriosis via openalex

[4] Correction to: Endometriosis and Adenomyosis: Global Perspectives Across the Lifespan via openalex

[5] Deficiency of MST1 in endometriosis related peritoneal macrophages promoted the autophagy of ectopic endometrial stromal cells by IL-10 via openalex

[6] Discovery of Phosphatidic Acid, Phosphatidylcholine, and Phosphatidylserine as Biomarkers for Early Diagnosis of Endometriosis via openalex

[7] Endometrial stromal cells treated by tumor necrosis factor‐α stimulate macrophages polarized toward M2 via interleukin‐6 and monocyte chemoattractant protein‐1 via openalex

[8] Endometriosis, a disease of the macrophage via openalex

[9] Endometriosis and Cancer: Exploring the Role of Macrophages via openalex

[10] Endometriosis-Associated Macrophages: Origin, Phenotype, and Function via openalex

[11] Endometriosis: epidemiology and aetiological factors via openalex

[12] Endometriosis Misdiagnosis via openalex

[13] Endometriosis Patients Show an Increased M2 Response in the Peritoneal CD14+low/CD68+low Macrophage Subpopulation Coupled with an Increase in the T-helper 2 and T-regulatory Cells via openalex

[14] Endometriosis through an immunological lens: a pathophysiology based in immune dysregulation via openalex

[15] Estrogen receptor β upregulates CCL2 via NF-κB signaling in endometriotic stromal cells and recruits macrophages to promote the pathogenesis of endometriosis via openalex

[16] Evaluation of M1 and M2 macrophages in ovarian endometriomas from women affected by endometriosis at different stages of the disease via openalex

[17] Expression of MMIF, HIF-1α and VEGF in Serum and Endometrial Tissues of Patients with Endometriosis via openalex

[18] Extracellular vesicles in endometrial-related diseases: role, potential and challenges via openalex

[19] Extracellular vesicles in endometriosis: role and potential via openalex

[20] Future Directions in Endometriosis Research and Therapeutics via openalex

[21] Future of Endometriosis Research via openalex

[22] G-CSF and IL-6 may be involved in formation of endometriosis lesions by increasing the expression of angiogenic factors in neutrophils via openalex

[23] Higher expression of vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 (Flk-1) and metalloproteinase-9 (MMP-9) in a rat model of peritoneal endometriosis is similar to cancer diseases via openalex

[24] Immunosuppressive Extracellular Vesicles as a Linking Factor in the Development of Tumor and Endometriotic Lesions in the Gynecologic Tract via openalex

[25] Inflammatory Mediators and Pain in Endometriosis: A Systematic Review via openalex

[26] Interleukin-33 modulates inflammation in endometriosis via openalex

[27] Intra-uterine microbial colonization and occurrence of endometritis in women with endometriosis† via openalex

[28] Involvement of the nuclear factor-κB pathway in the pathogenesis of endometriosis via openalex

[29] M1 Macrophage-Derived Nanovesicles Repolarize M2 Macrophages for Inhibiting the Development of Endometriosis via openalex

[30] Macrophages Are Alternatively Activated in Patients with Endometriosis and Required for Growth and Vascularization of Lesions in a Mouse Model of Disease via openalex

[31] Macrophages inhibit and enhance endometriosis depending on their origin via openalex

[32] MCP-1 exerts the inflammatory response via ILK activation during endometriosis pathogenesis via openalex

[33] Nuclear Factor-κB (NF-κB): An Unsuspected Major Culprit in the Pathogenesis of Endometriosis That Is Still at Large? via openalex

[34] Pathogenesis of Endometriosis: Role of Macrophages in Endometriosis via openalex

[35] Pelvic pain correlates with peritoneal macrophage abundance not endometriosis via openalex

[36] Rediscovering peritoneal macrophages in a murine endometriosis model via openalex

[37] Regulation of Inflammation Pathways and Inflammasome by Sex Steroid Hormones in Endometriosis via openalex

[38] Role of cytokines in endometriosis via openalex

[39] Roles of microRNAs in Regulating Apoptosis in the Pathogenesis of Endometriosis via openalex

[40] Serum and Ectopic Endometrium from Women with Endometriosis Modulate Macrophage M1/M2 Polarization via the Smad2/Smad3 Pathway via openalex

[41] Targeting delivery of mifepristone to endometrial dysfunctional macrophages for endometriosis therapy via openalex

[42] The Delicate Balance between the Good and the Bad IL-1 Proinflammatory Effects in Endometriosis via openalex

[43] The effects of resveratrol on the expression of VEGF, TGF-β, and MMP-9 in endometrial stromal cells of women with endometriosis via openalex

[44] The Essential Role of GATA6 in the Activation of Estrogen Synthesis in Endometriosis via openalex

[45] The Extracellular Vesicle–Macrophage Regulatory Axis: A Novel Pathogenesis for Endometriosis via openalex

[46] The Known, the Unknown and the Future of the Pathophysiology of Endometriosis via openalex

[47] The Role of Cytokines in Endometriosis* via openalex

[48] The Role of Peritoneal Macrophages in Endometriosis via openalex

[49] The role of small extracellular vesicle-miRNAs in endometriosis via openalex

[50] The role of TGF-β in the pathophysiology of peritoneal endometriosis via openalex

[51] Tumor necrosis factor alpha secretion by peritoneal macrophages in patients with endometriosis via openalex

[52] Understanding endometriosis from an immunomicroenvironmental perspective via openalex

[53] Unraveling pathogenesis, biomarkers and potential therapeutic agents for endometriosis associated with disulfidptosis based on bioinformatics analysis, machine learning and experiment validation via openalex

[54] VEGF Receptor 1-Expressing Macrophages Recruited from Bone Marrow Enhances Angiogenesis in Endometrial Tissues via openalex

[55] World Endometriosis Society consensus on the classification of endometriosis via openalex

[56] W6809509812 via openalex

[57] W1996123579 via openalex

[58] W2055348159 via openalex

[59] W2099944775 via openalex

[60] W2101278668 via openalex

[61] W2140246703 via openalex

[62] W2164385268 via openalex

[63] W2231237922 via openalex

[64] W2398274827 via openalex

[65] W2596152408 via openalex

[66] W2605484523 via openalex

[67] W2914782620 via openalex

[68] W2945953423 via openalex

[69] W2999016253 via openalex

[70] W3008724147 via openalex

[71] W3013522609 via openalex

[72] W3115000310 via openalex

[73] W3136714565 via openalex

[74] W3185900610 via openalex

[75] W3208517554 via openalex

[76] W4214754424 via openalex

[77] W4225871809 via openalex

[78] W4385475981 via openalex

[79] W4386542331 via openalex

[80] W4386987394 via openalex

[81] W4387306878 via openalex

[82] W4387427325 via openalex

[83] W4388406732 via openalex

[84] W4388692094 via openalex

[85] W4391812948 via openalex

[86] W4400585127 via openalex

[87] W4401383189 via openalex

[88] W4401574886 via openalex

[89] W4402607849 via openalex

[90] W4403922472 via openalex

[91] W4406020920 via openalex

[92] W4406334387 via openalex

[93] W1970087698 via openalex