Molecular Insights Into Endometriosis for Early Detection and Therapeutic Targets

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This review examines the molecular pathology of endometriosis, focusing on hormonal regulation, the endometrial microenvironment, immune dysregulation, and signaling pathways for biomarker and therapeutic target discovery.

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This paper reviews molecular pathological alterations in endometriosis, emphasizing how dysregulated sex hormone regulation, changes in the endometrial microenvironment, immune dysregulation, and multiple signaling pathways contribute to disease pathogenesis. It summarizes research progress on diagnostic biomarker candidates aimed at addressing the lack of reliable early detection tests and reviews therapeutic strategies targeting anti-proliferative/pro-apoptotic mechanisms and inflammatory responses. A key limitation stated is that, despite mechanistic advances, challenges remain in translating these discoveries into clinical applications and in yielding targeted management strategies. This paper is centrally about endometriosis — it focuses on molecular insights for early detection biomarkers and therapeutic targets in endometriosis.

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Abstract

Endometriosis is a hormone-dependent chronic inflammatory disease associated with pain and infertility, remains diagnostically and therapeutically challenging due to its multifactorial nature. Molecular mechanisms of the dynamic changes during disease pathogenesis may help identify potential diagnostic biomarkers and therapeutic targets. This paper reviews the molecular pathological alterations in endometriosis, focusing on the regulation of sex hormones, the endometrial microenvironment, immune dysregulation, and relevant signaling pathways. The lack of reliable early detection biomarkers significantly contributes to diagnostic delays. We summarize the research progress on biomarkers for endometriosis, providing the latest information on early diagnosis. We also review the therapeutic strategies targeting anti-proliferative/pro-apoptotic pathways and inflammatory responses. Although challenges persist in translating mechanistic discoveries into clinical applications, preclinical evidence suggests that addressing diagnostic delays and advancing innovative therapies may hold potential for yielding targeted management strategies for this complex disease.
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Abstract

Endometriosis is a hormone-dependent chronic inflammatory disease associated with pain and infertility, remains diagnostically and therapeutically challenging due to its multifactorial nature. Molecular mechanisms of the dynamic changes during disease pathogenesis may help identify potential diagnostic biomarkers and therapeutic targets. This paper reviews the molecular pathological alterations in endometriosis, focusing on the regulation of sex hormones, the endometrial microenvironment, immune dysregulation, and relevant signaling pathways. The lack of reliable early detection biomarkers significantly contributes to diagnostic delays. We summarize the research progress on biomarkers for endometriosis, providing the latest information on early diagnosis. We also review the therapeutic strategies targeting anti-proliferative/pro-apoptotic pathways and inflammatory responses. Although challenges persist in translating mechanistic discoveries into clinical applications, preclinical evidence suggests that addressing diagnostic delays and advancing innovative therapies may hold potential for yielding targeted management strategies for this complex disease. Similar content being viewed by others

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Funding The project supported by the Medical Scientific Research Foundation of Jiangsu Commission of Health (Grant No. K2024018), the Postgraduate Research & Practice Innovation Program of Jiangsu Province (grant number KYCX24_3922), and the COVID-19 Special Fund of the Affiliated Hospital of Jiangsu University (Grant No. Jdfyxgzx004). Author information Authors and Affiliations Contributions Mengmeng Kuai: Visualization, Validation, Resources, Investigation, Conceptualization. BaoHua Li: Writing-original draft, Visualization, Validation, Resources, Investigation, Conceptualization. ZiJun Shi: Resources, Project administration. QingTong Huang: Investigation, Conceptualization. Ye Pan: Resources. Min Tang: Supervision. Xuzhu Gao: Resources, Supervision. Jie Fang: Supervision. Peng Lü: Writing-review & editing, Validation, Supervision, Project administration, Funding acquisition. Corresponding authors Ethics declarations Declaration of Generative AI and AI-Assisted Technologies in the Writing Process According to the journal’s policy, we declare that during the preparation of this work, no AI tools were used for content creation, data analysis, or textual polishing; all core academic content and conclusions were independently developed, determined, and written by the authors. Data Sources and Search Strategy A systematic computerized search was conducted in electronic databases, including PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang Data, from their inception to March 2025. The search strategy was built around the core concept of "endometriosis" and combined with its key aspects, including "pathogenesis", "disease stage", "early diagnosis", "therapy"/"treatment", "targets", "Therapeutic Targets", "signaling pathways", "biomarker", "molecular mechanism", and "natural compounds". The search terms were applied to the title, abstract, and keyword fields, encompassing various synonymous expressions and related terms for these concepts. Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions Springer 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. About this article Cite this article Kuai, M., Li, B., Shi, Z. et al. Molecular Insights Into Endometriosis for Early Detection and Therapeutic Targets. Reprod. Sci. (2026). https://doi.org/10.1007/s43032-026-02124-5 Received: Accepted: Published: Version of record: DOI: https://doi.org/10.1007/s43032-026-02124-5

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