{"paper_id":"efc59b2b-1e3a-47e2-9241-85d47e2dd44a","body_text":"Abstract\nEndometriosis (EM) is a chronic inflammatory disorder characterized by the ectopic growth of endometrial-like tissue outside the uterine cavity. Its pathogenesis is closely linked to an imbalanced immune–inflammatory–angiogenic microenvironment. Core pathological features include immune suppression (e.g., M2 macrophage polarization, regulatory T cell increase), chronic inflammation (e.g., elevated IL-6, TNF-α, NF-κB/NLRP3 activation), and hypoxia-driven aberrant angiogenesis via the VEGF/HIF-1α axis. These components interact through shared molecular pathways—such as HIF-1α and NF-κB synergistically upregulating VEGF—forming a self-sustaining feedback loop that promotes lesion growth, fibrosis, pain, and infertility. Recent studies have explored microenvironment-targeted therapies (e.g., immune checkpoint blockade, anti-angiogenics), though most remain preclinical. Challenges include optimizing treatment timing, overcoming resistance, and patient heterogeneity. Future research should leverage multi-omics and organoid models to decode EM microenvironment dynamics and advance precision medicine.\nSimilar content being viewed by others\nData Availability\nNot applicable. This review synthesizes information from previously published studies, and no new datasets were generated.\nReferences\nTürkoğlu İ, Sacinti KG, Panattoni A, et al. Eating for optimization: unraveling the dietary patterns and nutritional strategies in endometriosis management. Nutr Rev. 2025;83(5):869–79. https://doi.org/10.1093/nutrit/nuae120.\nChen I, Veth VB, Choudhry AJ, et al. Pre- and postsurgical medical therapy for endometriosis surgery. Cochrane Database Syst Rev. 2020;11(11):Cd003678. https://doi.org/10.1002/14651858.CD003678.pub3.\nvan Hoesel MH, Chen YL, Zheng A, Wan Q, Mourad SM. Selective oestrogen receptor modulators (SERMs) for endometriosis. 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Adv Healthc Mater. 2021;10(12):e2100051. https://doi.org/10.1002/adhm.202100051.\nAcknowledgements\nWe sincerely thank our colleagues at Shandong Provincial Hospital Affiliated to Shandong First Medical University for their valuable support.\nFunding\nThe National Key R&D Program of China (2022YFC2704000); the Special foundation for Taishan Scholars (No. tstp20230657); the Major Basic Research of Natural Science Foundation of Shandong (ZR2021ZD34); the National Natural Science Foundation of China (grant numbers 82371653 and 82071621); and General Project of Shandong Natural Science Foundation ZR2023MH177.\nAuthor information\nAuthors and Affiliations\nContributions\nLiu Xiaoxuan: Writing– original draft. Wang Guoyun: Writing– review and editing.\nCorresponding author\nEthics declarations\nEthics Approval and Consent to Participate\nNot applicable.\nConsent for Publication\nNot applicable\nCompeting Interests\nThe authors declare that there are no conflicts of interest related to this article.\nAdditional information\nPublisher’s Note\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\nRights and permissions\nSpringer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.\nAbout this article\nCite this article\nLiu, X., Wang, G. Research Advances in the Endometriotic Microenvironment: Synergistic Immune–Inflammatory–Angiogenic Interactions and their Therapeutic Translation. Reprod. Sci. 33, 1–11 (2026). https://doi.org/10.1007/s43032-025-02017-z\nReceived:\nAccepted:\nPublished:\nVersion of record:\nIssue date:\nDOI: https://doi.org/10.1007/s43032-025-02017-z","source_license":"public-domain-us","license_restricted":false}