Neutrophil Extracellular Traps and Endometriosis: Insights from a Case-Control Study

Xu Z, Ji R, Wang M, Li T, Hu H
2025 · W7058463574
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This case-control study investigated whether neutrophil extracellular traps (NETs)–associated markers are linked to endometriosis by comparing 95 endometriosis patients with 95 controls. Researchers measured circulating free DNA (cf-DNA), nucleosomes, and neutrophil elastase (NE) in peripheral blood serum and/or neutrophils, including samples from ectopic and eutopic endometrium for the endometriosis group and eutopic endometrium for controls, and used ROC curve analysis to assess diagnostic discrimination. The endometriosis group had significantly higher cf-DNA, nucleosomes, and NE, with elevated NETs markers in patients with infertility and a positive correlation between pain severity and NETs marker levels. The paper notes that further studies are needed to explore the mechanisms connecting NETs markers with endometriosis, This paper is centrally about endometriosis — it evaluates NETs-associated markers as potential links to endometriosis and their associations with infertility and pain.

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Abstract

Zailong Xu,1,&ast; Rui Ji,2,&ast; Mei Wang,1 Tiantian Li,1 Hui Hu1 1Department of Obstetrics and Gynecology, Pudong New Area People’s Hospital in Shanghai, Shanghai, People’s Republic of China; 2Department of Obstetrics and Gynecology, Shanghai Sixth People’s Hospital, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Hu, Department of Obstetrics and Gynecology, Pudong New Area People’s Hospital in Shanghai, NO. 490 Chuanhuan South Road, Pudong New Area, Shanghai, 201200, People’s Republic of China, Email [email protected]: Endometriosis (EMS) is characterized by the occurrence, growth, infiltration, and recurrent bleeding of endometrial tissue outside the uterus. Recent studies have revealed a close association between Neutrophil Extracellular Traps (NETs) and the proliferation and metastasis of tumors. As EMS and tumours have similar biological behaviours, we hypothesised that key factors in tumourigenesis may also significantly influence the pathogenesis of EMS. Therefore, this study aimed to explore the potential link that exists between NETs and endometriosis.Methods: A total of 190 patients were selected and divided into control and endometriosis groups (95 patients each) based on inclusion and exclusion criteria. Samples from ectopic and eutopic endometrium in the experimental group, eutopic endometrium in the control group, and peripheral blood serum and neutrophils (PMN) were collected and analyzed. ROC curve analysis was used to evaluate the diagnostic ability of NETs-associated markers to differentiate endometriosis patients from controls.Results: The analysis of both patient groups revealed that levels of circulating free DNA (cf-DNA), nucleosomes, and neutrophil elastase (NE) were significantly higher in the experimental group compared to the controls. Further analysis indicated that the levels of NETs-related factors were elevated in patients with infertility and there was a positive correlation between pain severity and NETs markers in patients experiencing pain. Additionally, the ROC curve analysis demonstrated significant differences in cf-DNA, nucleosomes, and NE levels between the experimental and control groups (P < 0.05).Conclusion: NETs-associated markers may be linked to endometriosis, likely due to their involvement in tumor proliferation and metastasis, which share similarities with endometriosis. Further studies are needed to explore the mechanisms connecting endometriosis and NETs markers.Keywords: NETs, markers, endometriosis, infertility, case-control study
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International Journal of Women's Health (Jul 2025) Neutrophil Extracellular Traps and Endometriosis: Insights from a Case-Control Study Abstract Zailong Xu,1,* Rui Ji,2,* Mei Wang,1 Tiantian Li,1 Hui Hu1 1Department of Obstetrics and Gynecology, Pudong New Area People’s Hospital in Shanghai, Shanghai, People’s Republic of China; 2Department of Obstetrics and Gynecology, Shanghai Sixth People’s Hospital, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hui Hu, Department of Obstetrics and Gynecology, Pudong New Area People’s Hospital in Shanghai, NO. 490 Chuanhuan South Road, Pudong New Area, Shanghai, 201200, People’s Republic of China, Email [email protected]: Endometriosis (EMS) is characterized by the occurrence, growth, infiltration, and recurrent bleeding of endometrial tissue outside the uterus. Recent studies have revealed a close association between Neutrophil Extracellular Traps (NETs) and the proliferation and metastasis of tumors. As EMS and tumours have similar biological behaviours, we hypothesised that key factors in tumourigenesis may also significantly influence the pathogenesis of EMS. Therefore, this study aimed to explore the potential link that exists between NETs and endometriosis.Methods: A total of 190 patients were selected and divided into control and endometriosis groups (95 patients each) based on inclusion and exclusion criteria. Samples from ectopic and eutopic endometrium in the experimental group, eutopic endometrium in the control group, and peripheral blood serum and neutrophils (PMN) were collected and analyzed. ROC curve analysis was used to evaluate the diagnostic ability of NETs-associated markers to differentiate endometriosis patients from controls.Results: The analysis of both patient groups revealed that levels of circulating free DNA (cf-DNA), nucleosomes, and neutrophil elastase (NE) were significantly higher in the experimental group compared to the controls. Further analysis indicated that the levels of NETs-related factors were elevated in patients with infertility and there was a positive correlation between pain severity and NETs markers in patients experiencing pain. Additionally, the ROC curve analysis demonstrated significant differences in cf-DNA, nucleosomes, and NE levels between the experimental and control groups (P < 0.05).Conclusion: NETs-associated markers may be linked to endometriosis, likely due to their involvement in tumor proliferation and metastasis, which share similarities with endometriosis. Further studies are needed to explore the mechanisms connecting endometriosis and NETs markers.Keywords: NETs, markers, endometriosis, infertility, case-control study

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