Regulated cell death in endometrial diseases: from molecular mechanisms to targeted therapies

Regulated cell death (RCD) is a fundamental biological process essential for tissue homeostasis and disease regulation. Increasing evidence has demonstrated that RCD plays a pivotal role in the pathogenesis of uterine endometrial diseases, including endometriosis, abnormal decidualization, endometrial receptivity defects, and intrauterine adhesions. However, a comprehensive synthesis centered on the roles of RCD in endometrial diseases is still lacking. This review systematically summarizes the roles of various RCD pathways—apoptosis, autophagy, ferroptosis, pyroptosis, and cuproptosis—in endometrial diseases, emphasizing their interactions with hormonal signaling, molecular mechanisms in different endometrial cells, and cell–cell communication. It also evaluates therapeutic strategies targeting RCD, offering insights into potential interventions for diseases, such as endometriosis, intrauterine adhesion, and embryo implantation failure. Similar content being viewed by others Data availability This study did not generate or analyze any data.

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Hum Reprod Update 1(4):303–323 Funding This work was supported by the National Key Research and Development Program (No. 2024YFC2706900); National Natural Science Foundation grant of China (No. 82371647); The Science Foundation for Outstanding Youth of Liaoning Province (No. 2024JH3/50100023); Liaoning Revitalization Talents Program (No. XLYC1907071). Author information Authors and Affiliations Contributions DL, LH, and HZ designed and conceived the review. DZ, JS, NZ and TL wrote the manuscript. DZ, JL, JH, and ZN generated the figures. All the authors approved the final manuscript. Corresponding authors Ethics declarations Conflict of interest None. 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 Zi, D., Sun, J., Zuo, N. et al. Regulated cell death in endometrial diseases: from molecular mechanisms to targeted therapies. Arch Toxicol 100, 109–125 (2026). https://doi.org/10.1007/s00204-025-04192-z Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s00204-025-04192-z