image: Adenomyosis, marked by ectopic endometrial tissue, lacks effective models. Xu et al. develop an assembloid model replicating hormone responses and adenomyosis features. Single-cell analysis and further experiments revealed epithelial-stromal heterogeneity, disrupted BMP, enhanced WNT signaling, and increased immune and angiogenic activity. The model advances understanding of adenomyosis and therapeutic exploration.
Credit: Dr. Yiliang Xu from Tongji University.
Adenomyosis, a chronic hormone-dependent disorder, is characterized by the growth of endometrial tissue into the uterine muscle layer, accompanied by hypertrophy and proliferation of surrounding smooth muscle cells, ultimately leading to uterine enlargement. Affecting an estimated 20–35% of women of reproductive age, the condition is primarily associated with secondary dysmenorrhea, irregular menstruation, uterine enlargement, and reduced fertility. Progress in understanding its pathogenesis and developing preclinical therapies has long been hampered by the lack of reliable and accessible in vitro models.
Recently, a team led by Professor Xuan Che from the Affiliated Women and Children’s Hospital of Jiaxing University, in collaboration with Professor Shaorong Gao’s group at Tongji University, published a research article in SCIENCE CHINA Life Sciences titled “Decoding adenomyosis pathogenesis using an assembloid model.”
In this study, the researchers constructed an assembloid model that mimics the physiological structure of the endometrium and adenomyotic lesions by integrating primary endometrial organoids, stromal cells, and smooth muscle cells in vitro. Single-cell transcriptomic analysis confirmed that the model recapitulates transcriptional features consistent with in vivo tissue.
Notably, compared with assembloids derived from normal and eutopic endometrium, epithelial cells from lesion-derived assembloids in the secretory-like phase exhibited enhanced proliferative capacity and elevated expression of luminal epithelial signals, while glandular epithelial signals were comparatively downregulated. In addition, stromal cells from lesion-derived assembloids in the secretory-like phase showed a marked increase in the CRYAB+IL15+ subpopulation, whereas the BMP4+ subpopulation remained consistently reduced.
These findings suggest that the abnormal composition of stromal cell subpopulations in lesion-derived assembloids during the secretory-like phase may disrupt BMP/WNT signaling balance, thereby reshaping the downstream transcriptional profiles of epithelial cells. This novel assembloid system provides a promising platform for advancing mechanistic studies and accelerating preclinical drug discovery in adenomyosis.
Journal
Science China Life Sciences
Method of Research
Experimental study