Objective: Squamous cell carcinoma and adenocarcinoma in early-stage cervical cancer differ in biology and prognosis, yet current guidelines recommend uniform management. This study aimed to develop and internally validate histology-specific prognostic models for squamous cell carcinoma and adenocarcinoma to predict disease-free survival and overall survival, thereby supporting individualized adjuvant therapy for intermediate-risk cervical cancer. Methods: A multi-center retrospective analysis was conducted on patients with early-stage cervical cancer who underwent radical surgery without pathologic high-risk features. Patients were stratified into squamous cell carcinoma and adenocarcinoma cohorts. Histology-specific nomograms for disease-free survival and overall survival were developed using Cox regression and internally validated via 5-fold cross-validation. Model discrimination was assessed using the concordance index (C-index), and prognostic stratification using Kaplan-Meier analysis. Results: A total of 1053 patients with stage IB to IIA cervical cancer (911 squamous cell carcinoma, 142 adenocarcinoma) treated at 3 tertiary hospitals from 2005 to 2017 were included. Nomograms incorporating lymphovascular space involvement, stromal invasion, tumor size, and adjuvant therapy showed superior accuracy over Sedlis models (C-indices: 0.81/0.80 for disease-free survival/overall survival in squamous cell carcinoma; 0.91/0.96 for disease-free survival/overall survival in adenocarcinoma). Risk scores stratified patients into distinct prognostic sub-groups. In squamous cell carcinoma, high-risk patients had higher recurrence and mortality rates than low-risk patients (5-year recurrence rate: 11.7% vs 1.6%; mortality rate: 7.7% vs 0.6%). In adenocarcinoma, high-risk patients showed worse outcomes (5-year recurrence rate: 13.3% vs 0.0%; mortality rate: 6.1% vs 0.0%). Kaplan-Meier analysis confirmed significant survival differences across risk groups in both sub-types (all p < .05). Conclusions: Histology-specific nomograms incorporating intermediate-risk factors and adjuvant therapy effectively stratified prognostic sub-groups in early-stage cervical cancer, and may help inform risk-adapted post-operative management. Prospective external validation is needed for broader application.

Endometriosis affects approximately 10

Endometriosis is a common gynecologic disorder that can be considered in two major categories based on whether the endometrium invades the myometrium: adenomyosis, in which the endometrial glands and mesenchyme migrate into the myometrium, and endometriosis, in which the endometrial glands and mesenchyme migrate into organs other than the myometrium. Polypoid endometriosis is a rare form of endometriosis with imaging features of malignancy. In this article, we present a case of polypoid endometriosis in which a large amount of endometrium climbed to the abdominal surface of the plasma membrane layer of the uterus and grew toward the abdominal cavity, and we review the difficulties in the diagnosis and treatment of polypoid endometriosis and its association with autoimmune diseases, may provide a new idea for the accurate diagnosis and treatment of polypoid endometriosis in the future.

Endometriosis (EM) is driven by immune dysregulation and macrophage dysfunction, yet the underlying mechanisms remain unclear. Here, metabolomic profiling revealed excessive itaconate accumulation in EM lesions, primarily due to elevated cis-aconitate decarboxylase 1 (ACOD1) expression in ectopic stromal cells (ESCs). ESC-derived itaconate was internalized by peritoneal macrophages, where it suppressed pro-inflammatory activity and phagocytosis, thereby facilitating ESC survival and dissemination. Mechanistically, itaconate exerted dual regulatory effects on macrophages: it activated NRF2 signaling to repress the transcription of pro-inflammatory genes, and it enhanced lysosomal acidification, thereby reducing lysosomal calcium release, which in turn inhibited p38-MAPK activation and further attenuated pro-inflammatory gene expression. In vivo, ACOD1 inhibition restored macrophage function and reduced lesion burden, while exogenous 4-octyl itaconate aggravated disease progression. These findings define a novel "ESC-ACOD1-itaconate-macrophage" axis that mediates immunosuppression in EM and identify ACOD1 as potential therapeutic targets.

Efflux pumps confer antifungal resistance. Benzamidine (BM) conjugates overcome resistance by enhancing intracellular accumulation, but their cellular uptake mechanism remains unclear. A screen of membrane transport protein mutants revealed that plasma membrane transporters Alp1 and Nrt1 are importers of BM conjugates and are essential for their antifungal activity.

Background: The combination patterns of pathological intermediate-risk factors and the choice of adjuvant therapy for early-stage cervical cancer (CC) remain controversial. Objectives: To develop and validate nomogram-based prediction models incorporating pathological intermediate-risk factors to predict survival outcomes and optimize adjuvant therapy strategies in early-stage CC patients. Design: A multicenter retrospective study. Methods: A total of 1104 patients with stage IB-IIA CC who underwent primary surgical treatment and had no pathological high-risk factors were retrospectively enrolled from three tertiary medical centers in China between January 2005 and December 2017. Patients were randomly assigned to development and validation cohorts (approximately 3:1 ratio). Prognostic models for disease-free survival (DFS) and overall survival (OS) were developed by Cox proportional hazards regression and visualized using nomograms. Results: In this study, four prognostic models were developed incorporating different combinations of five key variables: lymphovascular space involvement (LVSI), stromal invasion (SI), tumor size (TS), histological type, and adjuvant therapy. Among these, Model 4 (LVSI + SI + TS + histological type + adjuvant therapy) demonstrated the highest discriminatory performance, with C-indices of 0.79 for both DFS and OS in the development cohort, and 0.84 for DFS and 0.77 for OS in the validation cohort. Model 4 also effectively stratified patients into prognostic risk groups in both cohorts, with high-risk patients exhibiting significantly worse DFS (development cohort: p < 0.0001; validation cohort: p = 0.0011) and OS (development cohort: p < 0.0001; validation cohort: p = 0.0036) compared to low-risk patients. Conclusion: The nomogram models developed in this study may provide individualized prognostic predictions for early-stage CC patients, potentially facilitating personalized decision-making regarding adjuvant therapy, though further validation in diverse patient cohorts and prospective studies is needed.

Tumor-associated macrophages (TAMs), the predominant immune cell population within the tumor immune microenvironment (TIME), play a vital role in promoting immune evasion and driving tumor progression. Beyond their well-established roles in reprogramming oncogenic signaling and silencing tumor suppressors, emerging evidence highlights that epigenetic modifications also critically shape the immunogenic landscape of tumors by modulating the phenotype and function of infiltrating immune cells. The TIME imposes persistent metabolic and inflammatory stressors-such as hypoxia, nutrient deprivation, and lactate accumulation-that profoundly influence the epigenetic and transcriptional states of TAMs, promoting their phenotypic plasticity and skewing them toward immunosuppressive, pro-tumoral phenotypes. Notably, this dynamic and reversible reprogramming closely parallels the defining features of epigenetic regulation, which is inherently sensitive to environmental stimuli and governs cellular identity. In this review, we comprehensively examine how extracellular cues within the TME rewire the expression and activity of key epigenetic regulators in TAMs, activate downstream signaling pathways, and reshape their molecular functions to reinforce tumor-supportive programs. Deciphering these epigenetic circuits provides a framework for therapeutic strategies aimed at re-educating TAMs toward anti-tumor phenotypes and enhancing the efficacy of immunotherapies.

RESEARCH QUESTION:Is surgery effective in decreasing iron deposition in the ovarian tissue surrounding an ovarian endometrioma? DESIGN:This cohort study was conducted in China between July 2023 and April 2024. Seventy-nine patients with ovarian endometriomas and 45 controls with other ovarian cyst types were enrolled. Magnetic resonance imaging using a relaxation sequence (MRI-R2*) has been proven to be a reliable method for detecting iron deposition. All participants underwent MRI-R2* preoperatively to detect the presence of iron in ovarian tissue, before surgical ovarian cystectomy. Additionally, patients with ovarian endometriosis underwent MRI-R2* 3 months after surgery. The end points were changes in iron content, as reflected by the R2* value of ovarian tissue, surrounding an ovarian endometrioma. RESULTS:The preoperative R2* value of the affected-side ovarian tissue in the ovarian endometriosis group was significantly higher than that in the control group (27.00 [22.50-32.25] Hz versus 23.00 [13.50-26.36] Hz; P = 0.012). In the ovarian endometriosis group, the affected-side ovarian tissue had higher R2* values than the intact side ovarian tissue before (27.00 [22.50-32.25] Hz versus 19.19 [14.43-24.12] Hz; P = 0.019) and after (27.13 [21.80-31.50] Hz versus 21.96 [19.00-27.53] Hz; P = 0.015) surgery. No significant changes were observed in the R2* values of the affected-side ovarian tissue after surgery. CONCLUSIONS:In patients with ovarian endometriomas, the affected-side ovarian tissue demonstrated no reduction in iron content within 3 months of ovarian cystectomy. Cystectomy alone is inadequate for complete elimination of local iron deposition. Serial MRI-R2* monitoring could serve as an objective modality for assessing postoperative iron deposition dynamics.

Endometriosis (EM) exhibits localised iron overload. However, the contribution of ferroptosis to EM pathogenesis remains unclear. We investigated how iron overload affects CD8⁺ T cell immune function and the underlying ferroptotic mechanisms. We collected eutopic and ectopic endometrial tissues from 57 patients with stage III–IV EM and eutopic tissues from 31 controls. Iron deposition was assessed by Prussian blue staining; CD8⁺ T cell infiltration by immunohistochemistry; and ferroptosis in CD8⁺ T cells by immunofluorescence and flow cytometry. In vitro and in vivo assays measured CD8⁺ T cell ferroptosis and endometrial stromal cell apoptosis via flow cytometry. Transwell assays evaluated cell migration. Gene and protein expression were analysed via RT-qPCR and Western Blot. We verified the effect of iron overload on the growth of lesions in vivo by constructing a mouse EM model. The role of CD8⁺ T cells in EM progression was tested using a reinfusion model. In ectopic EM lesions, CD8⁺ T cells were enriched yet functionally impaired, showing increased ferrous iron accumulation and lipid peroxidation alongside decreased GPX4 expression. In vitro, iron overload reduced CD8⁺ T cell viability, elevated lipid peroxidation, and induced mitochondrial damage—effects reversed by ferroptosis inhibitors. Iron overload upregulated p53 and downregulated xCT and GPX4; p53 inhibition blocked ferroptosis, indicating a p53-dependent pathway. In vivo EM models confirmed that excess iron compromises CD8⁺ T cell function and impairs their recruitment to lesion sites. Iron overload induces p53-mediated inhibition of xCT/GPX4, triggering ferroptosis in CD8⁺ T cells and leading to their dysfunction. These insights into ferroptosis–CD8⁺ T cell interactions in EM may guide the development of novel immunotherapeutic strategies.

Endometriosis diagnosis is usually delayed. The gold standard for diagnosing endometriosis is laparoscopy, which is invasive and accompanied by several risks. Currently, there are no effective non-invasive biomarkers for diagnosing endometriosis. Here, we investigated whether metabolites whose levels are altered in patients with endometriosis hold potential as diagnostic biomarkers for the disease. This case-control study involved 32 patients with endometriosis and 29 patients with other benign gynecological disease. The diagnosis of all patients was confirmed through postoperative histopathological examination, and the patients were divided into two groups: an endometriosis group (EM) and a control group. Fasting blood was collected and used for non-targeted metabolomic-based detection. The data were processed through principal component analysis, orthogonal partial least squares discriminant analysis, and significance analysis of microarrays. A univariate receiver operating characteristic curve was used to evaluate the diagnostic value of the metabolites. The metabolite profiles of patients with endometriosis were markedly different compared with those of the controls. In addition, several metabolic pathways, including biosynthesis of unsaturated fatty acids, arginine biosynthesis, and glutathione metabolism, were altered. Ornithine and medorinone showed better potential as biomarkers for endometriosis diagnosis than CA125. We analyzed the altered metabolic profiles in patients with endometriosis and found ornithine and medorinone as potential non-invasive biomarkers for endometriosis diagnosis, whereas the combined ornithine-medorinone diagnosis is more valuable. These findings may help advance research on non-invasive diagnostic biomarkers for endometriosis. Further research with an improved study design and a larger cohort should be performed to confirm the diagnostic potential and clinical application of these biomarkers.

ObjectiveWe carried out this study to explore the possibility of initiating goserelin therapy during the non-menstrual period in patients diagnosed with adenomyosis.Methods115 premenopausal adenomyosis patients were enrolled and divided into three groups based on their menstrual cycle phase during the initial outpatient visit: menstrual, follicular, and luteal. Each received a 3.6 mg subcutaneous dose of goserelin monthly for three months. The endpoints encompassed alterations in uterine volume, dysmenorrhea Numerical Rating Scale (NRS) score, CA125 level, hemoglobin (HGB) after a 12-week treatment course, and the occurrence and duration of uterine hemorrhage during the first treatment cycle.ResultsAnalysis revealed that the timing of goserelin therapy initiation in the menstrual cycle did not significantly impact its effectiveness in reducing uterine size, alleviating pain, lowering CA125 levels, or improving hemoglobin concentrations. However, patients starting treatment during the luteal phase experienced increased uterine bleeding (reference: menstrual period, OR = 4.33, 95% CI 1.23-15.25, p = .023).ConclusionsThe results suggested non-inferiority of goserelin therapy initiated during the non-menstrual period, but the uterine bleeding rate was higher in the luteal phase group. Therefore, goserelin treatment for outpatient adenomyosis patients should not be limited to starting during the menstrual period; it can also be initiated outside the menstrual period, providing more convenience for patients as most consultations occur outside the menstrual period. However, the use of goserelin during the luteal phase should be avoided to reduce the risk of exacerbated bleeding, especially in anemic patients with heavy menstrual bleeding. This study highlights the importance of individualizing treatment initiation based on the patient's health profile to optimize therapeutic outcomes and minimize adverse effects.Trial registrationChiCTR2200059548

BackgroundAdenomyosis is a commonly observed benign gynecological disease that affects the quality of life and social psychology of women of childbearing age. However, because of the unknown etiology and incidence of adenomyosis, its pathophysiological mechanism remains unclear; further, because no noninvasive, accurate, and individualized diagnostic methods are available, treatment and efficacy evaluations are limited. Notably, the interaction between the changes in the microecological environment of the female reproductive tract and human immunity, endocrine, and other links leads to the occurrence and development of diseases. In addition, the vaginal microbiome differs in different menstrual cycles; therefore, assessing the differences between the microbiomes of patients with adenomyosis and healthy individuals in different menstrual cycles will improve the understanding of the disease and provide references for the search for noninvasive diagnosis and individualized precision treatment of adenomyosis. This study aimed to explored the data of individuals in different menstrual cycles.ResultsDifferences in the vaginal microbiome between patients with adenomyosis and healthy individuals were observed. At phylum level, the relative abundance of Firmicutes in the adenomyosis group was higher than that in the control group, which contributed the most to the species difference between the two groups. At the genus level, Lactobacillus was the most dominant in both groups, Alpha-diversity analysis showed significant differences in the adenomyosis and control group during luteal phase (Shannon index, p = 0.0087; Simpson index, p = 0.0056). Beta-diversity index was significantly different between the two groups (p = 0.018). However, based on Weighted Unifrac analysis, significant differences were only observed throughout the luteal phase (p = 0.0146). Within the adenomyosis group, differences between women with different menstrual cycles were also observed. Finally, 50 possible biomarkers including were screened and predicted based on the random forest analyse.ConclusionsThe vaginal microbiome of patients with adenomyosis and healthy individuals differed during menstrual periods, especially during the luteal phase. These findings facilitate the search for specific biological markers within a limited range and provide a more accurate, objective, and individualized diagnostic and therapeutic evaluation method for patients with adenomyosis, compared to what is currently available.

This review comprehensively explores the complex role of copper homeostasis in female reproductive system diseases. As an essential trace element, copper plays a crucial role in various biological functions. Its dysregulation is increasingly recognized as a pivotal factor in the pathogenesis of gynecological disorders. We investigate how copper impacts these diseases, focusing on aspects like oxidative stress, inflammatory responses, immune function, estrogen levels, and angiogenesis. The review highlights significant changes in copper levels in diseases such as cervical, ovarian, endometrial cancer, and endometriosis, underscoring their potential roles in disease mechanisms and therapeutic exploration. The recent discovery of 'cuproptosis,' a novel cell death mechanism induced by copper ions, offers a fresh molecular perspective in understanding these diseases. The review also examines genes associated with cuproptosis, particularly those related to drug resistance, suggesting new strategies to enhance traditional therapy effectiveness. Additionally, we critically evaluate current therapeutic approaches targeting copper homeostasis, including copper ionophores, chelators, and nanoparticles, emphasizing their emerging potential in gynecological disease treatment. This article aims to provide a comprehensive overview of copper's role in female reproductive health, setting the stage for future research to elucidate its mechanisms and develop targeted therapeutic strategies.

The pathogenesis of adenomyosis is closely related to the epithelial-mesenchymal transition and macrophages. MicroRNAs have been extensively investigated in relation to the epithelial-mesenchymal transition in a range of malignancies. However, there is a paucity of research on extracellular vesicles derived from the eutopic endometrium of adenomyosis and their encapsulated microRNAs. In this study, we investigated the role of microRNA-25-3p derived from extracellular vesicles in inducing macrophage polarization and promoting the epithelial-mesenchymal transition in endometrial epithelial cells of patients with adenomyosis and controls. We obtained eutopic endometrial samples and isolated extracellular vesicles from the culture supernatant of primary endometrial cells. Real-time quantitative PCR analysis demonstrated that microRNA-25-3p was highly expressed in extracellular vesicles, as well as in macrophages stimulated by extracellular vesicles from eutopic endometrium of adenomyosis; and macrophages transfected with microRNA-25-3p exhibited elevated levels of M2 markers, while displaying reduced levels of M1 markers. After co-culture with the above polarized macrophages, endometrial epithelial cells expressed higher levels of N-cadherin and Vimentin, and lower protein levels of E-cadherin and Cytokeratin 7. It was revealed that microRNA-25-3p encapsulated in extracellular vesicles from eutopic endometrial cells could induce macrophage polarization toward M2, and the polarized macrophages promote epithelial-mesenchymal transition in epithelial cells. However, in vitro experiments revealed no significant disparity in the migratory capacity of endometrial epithelial cells between the adenomyosis group and the control group. Furthermore, it was observed that microRNA-25-3p-stimulated polarized macrophages also facilitated the epithelial-mesenchymal transition and migration of endometrial epithelial cells within the control group. Thus, the significance of microRNA-25-3p-induced polarized macrophages in promoting the development of adenomyosis is unclear, and macrophage infiltration alone may be adequate for this process. We emphasize the specificity of the local eutopic endometrial microenvironment and postulate its potential significance in the pathogenesis of adenomyosis.

BACKGROUND:Adenomyosis is a benign disorder characterized by the presence of ectopic endometrial glands and stroma within the myometrium. The main clinical manifestations of adenomyosis are dysmenorrhea, menorrhagia, and infertility, which affect patients' quality of life. Recently, with advancements in imaging techniques, magnetic resonance imaging, and ultrasonography have become the main diagnostic tools for adenomyosis. In addition to the diagnosis and differential diagnosis of adenomyosis, ultrasonography can also be used to evaluate the severity of adenomyosis. The emergence of new techniques, such as elastography and contrast-enhanced ultrasonography (CEUS), has significantly improved the accuracy of ultrasound-based diagnosis of adenomyosis. These two imaging tools can also be used for the differential diagnosis of adenomyosis and the evaluation of treatment efficacy after medication or ablation procedure.OBJECTIVE:we review the efficacy of ultrasonography as a diagnostic tool for adenomyosis. We also aim to introduce the potential of ultrasound imaging in the evaluation of the severity of this disease, as well as the application of elastography and contrast-enhanced ultrasonography (CEUS) in its diagnosis.RESULTS AND CONCLUSION:Our findings reveal the potential value of ultrasonography combined with elastography and/or CEUS as medication guidance and efficacy evaluation tools in the long-term management of adenomyosis.

Abstract Endometriosis is an inflammatory disease with non-specific symptoms, including chronic pelvic pain and infertility, which affects thousands of women of reproductive age. Early diagnosis of endometriosis remains challenging. We aimed to build a diagnostic model based on m6A methylation-related genes to provide a new perspective on the clinical diagnosis of endometriosis. Two datasets from previous endometriosis studies were selected. GSE51981 was for training and GSE7305 was for validation. The expression of m6A methylation-related genes between proliferative eutopic endometrium from women with and without endometriosis was compared. Most m6A methylation-related genes were down-regulated in eutopic endometrium from women with endometriosis than those without it. The random forest classifier identified 5 significant differentially expressed genes (YTHDF2, NKAP, FTO, ZCCHC4 and HNRNPC) that might be involved in the development of endometriosis by affecting miRNA maturation or immune cell infiltration. These genes were included in a logistic regression to construct a new diagnostic model for endometriosis with an area under the ROC curve of 0.852. The model was tested on another independent dataset（AUC 0.750）and not only diagnosed endometriosis well but also showed how severe it was. We also found that YTHDF2 was very good at diagnosing endometriosis on its own and was correlated with macrophage and neutrophil infiltration that may be important for endometriosis development. In conclusion, this novel diagnostic model using m6A methylation-related genes may be a new method for early non-invasive diagnosis of endometriosis.

The management of endometriosis has been complicated by the COVID-19 pandemic. We aimed to introduce the establishment and application of a new follow-up method during the COVID-19 pandemic-the electronic follow-up (e-follow-up) platform for endometriosis-and to test the applicability of the platform-based follow-up management model and patient satisfaction. We used the platform for information entry and post-operative follow-up of 152 patients with endometriosis from January 2021 to August 2022, and compared patients' Zung's Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS), and Visual Analogue Score (VAS) (range: 0 - 10, indicating: no pain-extreme pain) scores preoperatively and after 6-month of follow-up, together with recording patients' follow-up satisfaction and number of recurrence of lesions. Eventually, the SDS, SAS, and VAS scores were significantly lower than those at pre-surgery (p < .001), and the follow-up satisfaction rate reached 100%, with 91.41% expressing great satisfaction. The cumulative number of recurrences was 2 out of 138. Follow-up using this platform reduce the risk of COVID-19 transmission, enabled more efficient access to healthcare resources for patients with endometriosis, improved the efficiency of follow-up management, met the mental health needs of the patients.

Research question: Does iron overload in patients with endometriosis affect ovarian function? Can a method be developed to visually reflect this?Design: Magnetic resonance imaging (MRI) R2* was used to evaluate the correlation between iron deposition of ovarian and antiMueurollerian hormone (AMH) in patients with endometriosis. All patients underwent T2* MRI scanning. Serum AMH levels were measured preoperatively. The area of focal iron deposition, iron content of the cystic fluid and AMH levels between the endometriosis and control groups were compared using non-parametric tests. The effects of iron overload on AMH secretion in mouse ovarian granulosa cells were investigated by adding different concentrations of ferric citrate to the medium.Results: A significant difference was found between endometriosis and control groups in area of iron deposition (P < 0.0001), cystic fluid iron content (P < 0.0001), R2* of lesions (P < 0.0001) and R2* of the cystic fluid (P < 0.0001). Negative correlations were found between serum AMH levels and R2* of cystic lesions in patients with endometriosis aged 18-35 years (rs =-0.6484, P < 0.0001), and between serum AMH levels and R2* of cystic fluid (rs =-0.5074, P = 0.0050). Transcription level (P < 0.0005) and secretion level (P < 0.005) of AMH significantly decreased with the increase in iron exposure.Conclusion: Iron deposits can impair ovarian function, which is reflected in MRI R2*. Serum AMH levels and R2* of cystic lesions or fluid in patients aged 18-35 years had a negative correlation with endometriosis. R2* can be used to reflect the changes of ovarian function caused by iron deposition.

The development of endometriosis is closely linked to macrophages, and the type M1 macrophage has been hypothesized to play an inhibitory role in its progression. Escherichia coli induces macrophage polarization toward M1 in numerous diseases and differs in the reproductive tract of patients with and without endometriosis; however, its specific role in endometriosis development remains unknown. Therefore, in this study, E. coli was selected as a stimulator to induce macrophages, and its effects on the growth of endometriosis lesions in vitro and in vivo were investigated using C57BL/6N female mice and endometrial cells. It was revealed that E. coli inhibited the migration and proliferation of co-cultured endometrial cells by IL-1 in vitro and prevented the growth of lesions and induced macrophage polarization toward M1 in vivo. However, this change was counteracted by C-C motif chemokine receptor 2 inhibitors, suggesting that it was associated with bone marrow-derived macrophages. Overall, the presence of E. coli in the abdominal cavity may be a protective factor for endometriosis.

Adenomyosis is a benign disease, but it exhibits a metastatic property similar to tumors. Its pathogenesis is still unclear. One theory is that adenomyosis is the result of epithelial-mesenchymal transition (EMT) in displaced embryonic Muller cells. Macrophages accumulate in the eutopic endometrium of adenomyosis and play an important role in EMT and the pathogenesis of adenomyosis. Extracellular vesicles (EVs) are considered an important mechanism of intercellular communication, but few studies have shown the role of EVs between endometrial epithelial cells and macrophages. In this study, we collected the eutopic endometrium of adenomyosis, and acquired the primary endometrial cells, then isolated EVs from the culture supernatants. We identified the characteristics of EVs by transmission electron microscopy, nanoparticle tracking, and western blot, and then detected the mRNA expression levels of CD163, IL-10, iNOS, and TNF-α in macrophages by qRT-PCR after co-cultured with EVs; the expression levels of E-cadherin, CK7, N-cadherin, and Vimentin by Western blot, and the migration abilities of epithelial cells by Transwell assay. The results showed that macrophages were highly expressed in the mRNA levels of CD163, IL10, and TNF-α after treated by EVs from adenomyosis patients; endometrial epithelial cells expressed lower protein levels of E-cadherin and CK7, higher levels of N-cadherin and Vimentin after co-cultured with the above polarized macrophages; and the migration abilities of epithelial cells were enhanced. In conclusion, EVs derived from adenomyosis can induce macrophages to polarize toward M2b, and the polarized macrophages could, in turn, induce EMT process in endometrial epithelial cells.