Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education (MOE), West China Second University Hospital, Sichuan University, Chengdu, China.
Deep Underground Space Medical Center, West China Hospital, Sichuan University, Chengdu, China.
Front Immunol. 2023 Feb 20;14:1084516. doi: 10.3389/fimmu.2023.1084516. eCollection 2023.
In the pathology of pelvic organ prolapse (POP), little is known about the contributing role of pelvic microenvironment. Also, the age-related differences in pelvic microenvironment of POP patients is always ignored. In the present study, we investigated the age-related differences in pelvic microenvironment between Young POP patients and Old POP patients, and the novel cell types and critical regulators which contributes to the age-related differences.
Single-cell transcriptomic analyses were used to detect the changes in cell composition and gene expression from the pelvic microenvironment of control group (<60 years), Young POP group (<60 years) and Old POP group (>60 years). Then, immunohistochemistry and immunofluorescence were used to verify the novel cell types and critical regulators in the pelvic microenvironment. Furthermore, histopathological alteration and mechanical property alteration in POP with different ages were revealed by vaginal tissue histology and biomechanical testing.
The up-regulated biological process in Old women with POP is mainly related to chronic inflammation, while the up-regulated biological process in Young women with POP is mainly related to extracellular matrix metabolism. Meantime, CSF3+ endothelial cells and FOLR2+ macrophages were found to play a central role in inducing pelvic chronic inflammation. Furthermore, the collagen fiber and mechanical property of POP patients decreased with aging.
Taken together, this work provides a valuable resource for deciphering the aging-related immune cell types and the critical regulators in pelvic microenvironment. With better understanding of normal and abnormal events in this pelvic microenvironment, we provided rationales of personalized medicine for POP patients with different ages.
在盆腔器官脱垂（POP）的病理学中，对于盆腔微环境的致病作用知之甚少。此外，POP 患者的盆腔微环境的年龄相关性差异也常常被忽视。在本研究中，我们研究了年轻 POP 患者和老年 POP 患者的盆腔微环境的年龄相关性差异，以及导致这种差异的新的细胞类型和关键调节因子。
使用单细胞转录组分析检测了来自对照组（<60 岁）、年轻 POP 组（<60 岁）和老年 POP 组（>60 岁）的盆腔微环境中细胞组成和基因表达的变化。然后，使用免疫组织化学和免疫荧光技术验证了盆腔微环境中的新的细胞类型和关键调节因子。此外，通过阴道组织病理学和生物力学测试揭示了不同年龄 POP 的组织学改变和力学特性改变。
老年 POP 女性中上调的生物学过程主要与慢性炎症有关，而年轻 POP 女性中上调的生物学过程主要与细胞外基质代谢有关。同时，CSF3+内皮细胞和 FOLR2+巨噬细胞被发现在内脏慢性炎症的诱导中起着核心作用。此外，POP 患者的胶原纤维和力学性能随年龄增长而下降。
综上所述，这项工作为解析盆腔微环境中与衰老相关的免疫细胞类型和关键调节因子提供了有价值的资源。通过更好地理解这个盆腔微环境中的正常和异常事件，我们为不同年龄的 POP 患者提供了个性化医疗的依据。
