Li Chenchen, Tan Xiyang, Deng Dashi, Kong Chenfan, Feng Lida, Wang Weijing, Lin Kaida, Li Yuqing, Lei Qifang, Liu Lisha, Tao Tao, Pan Ruile, Li Guangzhi, Wu Song
Institute of Urology, The Affiliated Luohu Hospital of Shenzhen University, Shenzhen, 518000, P. R. China.
Shenzhen Hospital, Shanghai University of Traditional Chinese Medicine, Shenzhen, Guangdong, 518004, China.
Adv Mater. 2024 Sep;36(39):e2407750. doi: 10.1002/adma.202407750. Epub 2024 Aug 8.
Thin endometrium (TE) is closely associated with infertility in reproductive medicine. Estrogen therapy gains unsatisfactory outcomes. In this study, an artificial mucus based on dopamine (L-DOPA)-modified hyaluronic acid combining phytoestrogen cajaninstilbene acid and rat urinary exosomes (CUEHD) is constructed for TE treatment using a rat TE model. In the rat TE model, the dominant elastic behavior and adhesive properties of CUEHD guarantee adequate retention, rendering superior synergistic treatment efficacy and favorable biosafety characteristics. CUEHD treatment significantly increases endometrial thickness and promotes receptivity and fertility. Mechanistically, estrogen homeostasis, inflammation inhibition, and endometrial regeneration are achieved through the crosstalk between ER-NLRP3-IL1β and Wnt-β catenin-TGFβ-smad signaling pathways. Moreover, the therapeutic potential of exosomes from human urine and adipose tissue-derived stem cells (ADSCs) and rat ADSCs are also demonstrated, indicating extensive use of the artificial mucus system. Thus, this study illustrates a platform combining phytoestrogen and exosomes with promising implications for TE treatment.
薄型子宫内膜（TE）在生殖医学中与不孕症密切相关。雌激素治疗效果不理想。在本研究中，使用大鼠TE模型构建了一种基于多巴胺（L-DOPA）修饰的透明质酸、结合植物雌激素鹰嘴豆芽素A和大鼠尿液外泌体（CUEHD）的人工黏液用于TE治疗。在大鼠TE模型中，CUEHD的主要弹性行为和黏附特性保证了足够的滞留，呈现出卓越的协同治疗效果和良好的生物安全性特征。CUEHD治疗显著增加子宫内膜厚度并促进接受性和生育能力。机制上，通过ER-NLRP3-IL1β和Wnt-β连环蛋白-TGFβ-smad信号通路之间的相互作用实现雌激素稳态、炎症抑制和子宫内膜再生。此外，还证明了人尿液和脂肪组织来源干细胞（ADSC）以及大鼠ADSC的外泌体的治疗潜力，表明该人工黏液系统具有广泛的应用前景。因此，本研究阐明了一个结合植物雌激素和外泌体的平台，对TE治疗具有广阔的应用前景。
