使用所谓的组合体创建一种新颖、更先进的人类子宫内膜体外模型，探索子宫腺肌症中的子宫内膜容受性。通过免疫组织化学、ELISA 和扫描电子显微镜 (SEM) 评估组合体对激素刺激的反应性。基于大学妇科研究单位。12 名女性，其中 6 名患有子宫腺肌病。从子宫内膜活检中收集类器官（以腺体碎片的形式）和基质成纤维细胞。这两个群体在细胞外基质内组合以创建 3D 组装体，然后将其暴露于激素刺激（β-雌二醇 48 小时，然后 β-雌二醇/孕酮/环磷酸腺苷 72 小时）以模拟植入窗口甘氨肽、白血病抑制因子 (LIF) 和同源盒 A10 (HOXA10) 表达、催乳素分泌和胞饮足发育。成功从患有和不患有子宫腺肌症的女性中分离出子宫内膜类器官和基质细胞，并将其组合生成装配体模型。经刺激后，两组的组装体获得了更多的分泌期样表型，如组织学所示，并且通过免疫组织化学显示甘肽蛋白、LIF 和 HOXA10 呈阳性。刺激后，腺肌组合体在基质室内表达的 LIF 和 HOXA10 水平显着低于相同条件下的健康组合体。 ELISA 揭示了体外催乳素的分泌，显示健康女性和受影响女性的激素处理后的组合体呈上升趋势。通过扫描电镜，刺激后在健康组合体的上皮表面上可以识别出完全形成的胞足体，但在子宫腺肌病的情况下则不存在。可以从健康受试者和受子宫腺肌病影响的女性的子宫内膜活检中产生初级组合体。这些组合体易于受到激素刺激，并模仿体内子宫内膜组织的分泌期特异性特征，包括甘肽、LIF 和 HOXA10 表达以及胞饮足形成。来自子宫腺肌病的组合体似乎对激素治疗不太敏感，显示间质室中 LIF 和 HOXA10 的表达减少，并且无法形成胞饮足。总而言之，子宫内膜组合体可以作为子宫腺肌病相关子宫内膜容受性受损的先进临床前模型，为理解和治疗该疾病开辟新视野。版权所有 © 2024。由爱思唯尔公司出版。

To create a novel, more advanced in vitro model of human endometrium, using so-called assembloids, looking to explore endometrial receptivity in adenomyosis.Evaluation of assembloid responsiveness to hormonal stimulation by immunohistochemistry, ELISA and scanning electron microscopy (SEM).University-based research unit in gynecology.Twelve women, 6 of whom were affected by adenomyosis.Organoids (in the form of glandular fragments) and stromal fibroblasts were collected from endometrial biopsies. The two populations were combined inside an extracellular matrix to create 3D assembloids, which were then exposed to hormonal stimulation (β-estradiol for 48 hours, followed by β-estradiol/progesterone/cyclic adenosine monophosphate for 72 hours) to mimic the window of implantation.Glycodelin, leukemia inhibitory factor (LIF) and homeobox A10 (HOXA10) expression, prolactin secretion and pinopode development.Endometrial organoids and stromal cells were successfully isolated from women with and without adenomyosis and combined to generate the assembloid model. Upon stimulation, assembloids from both groups acquired a more secretory phase-like phenotype, as demonstrated by histology, and were shown to be positive for glycodelin, LIF and HOXA10 by immunohistochemistry. Adenomyotic assembloids expressed significantly lower levels of LIF and HOXA10 within the stromal compartment after stimulation than did healthy assembloids in the same condition. ELISA revealed prolactin secretion in vitro, showing an upward trend in hormonally treated assembloids from both healthy and affected women. By SEM, fully formed pinopodes were discerned on the epithelial surface of healthy assembloids after stimulation, but they were absent in case of adenomyosis.Primary assembloids can be generated from endometrial biopsies from both healthy subjects and women affected by adenomyosis. These assembloids are amenable to hormonal stimulation and mimic secretory phase-specific characteristics of endometrial tissue in vivo, including glycodelin, LIF and HOXA10 expression, and pinopode formation. Assembloids from adenomyosis appear to be less sensitive to hormonal treatment, showing reduced expression of LIF and HOXA10 in the stromal compartment and failing to form pinopodes. All in all, endometrial assembloids may serve as an advanced preclinical model of adenomyosis-related impaired endometrial receptivity, opening up new horizons in understanding and treating the condition.Copyright © 2024. Published by Elsevier Inc.