Decoding adenomyosis pathogenesis using an assembloid model

Adenomyosis remains a challenging gynecological disorder to investigate due to the absence of in vitro models that accurately replicate endometrial tissue dynamics across the menstrual cycle. To address this gap, we established an endometrial assembloid model that faithfully mimics cycle-dependent endometrial responses and captures key cellular and molecular hallmarks of adenomyosis, including ectopic lesion- specific epithelial and stromal heterogeneity. Single-cell transcriptomics revealed that ectopic epithelial cells shift toward a luminal- dominant, glandular-deficient transcriptional profile during the secretory-like phase. This transition correlated with ectopic stromal reorganization—specifically, loss of BMP4+ stromal cells and an accumulation of CRYAB+IL15+ stromal cells—which impaired BMP-mediated stromal-epithelial signaling while enhancing WNT activation. Additionally, ectopic epithelial and stromal cells demonstrated increased immunity and angiogenesis activities. Our assembloid platform not only provides a physiologically relevant model for investigating adenomyosis pathogenesis but also implicates aberrant WNT signaling as a potential therapeutic target, offering new opportunities for mechanism-driven treatment strategies. Similar content being viewed by others Data availability The raw sequence data reported in this paper have been deposited in the Genome Sequence Archive in the National Genomics Data Center, China National Center for Bioinformation/Beijing Institute of Genomics, Chinese Academy of Sciences (GSA-Human: HRA009550) that are publicly accessible at https://ngdc.cncb.ac.cn/gsa-human. This paper does not report custom code. Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

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This work was supported by the National Natural Science Foundation of China (82488101 to S.G), the National Key Research and Development Program of China (2023YFA1800300 to X.X., 2023YFA1801800 to L.W., 2022YFC2702200 to S.G.), the National Natural Science Foundation of China (82471684 to X.C., 32330030 to S.G., 32270840 to L.W., 32270908 to X.X.), Science and Technology Commission of Shanghai Municipality (23JC1403700), Shanghai Key Laboratory of Maternal-Fetal Medicine (mfmkf202201), and the Natural Science Foundation of Zhejiang Province (LTGY24H040002). We would like to thank our laboratory colleagues for their assistance with experiments and advice. Author information Authors and Affiliations Corresponding authors Ethics declarations The authors declare that they have no conflict of interest. This work was approved by the Scientific Research Ethics Committee of the Jiaxing University Affiliated Maternity and Child Hospital (No. 2021-65). Supplemental Information Rights and permissions About this article Cite this article Xu, Y., Cheng, T., Wang, J. et al. Decoding adenomyosis pathogenesis using an assembloid model. Sci. China Life Sci. 69, 136–150 (2026). https://doi.org/10.1007/s11427-025-2981-1 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s11427-025-2981-1