Li Ping, Jian Yu, Liu Xinyi, Pan Li, Tan Zhihui, Shan Nianchun
Department of Obstetrics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People's Republic of China.
Hunan Engineering Research Center of Early Life Development and Disease Prevention, Changsha, 410008, Hunan, People's Republic of China.
Sci Rep. 2025 Apr 29;15(1):15107. doi: 10.1038/s41598-025-97433-1.
Intrauterine adhesions (IUAs) are a complex condition that frequently results in menstrual disturbances, infertility, and obstetric complications. Unfortunately, the underlying pathophysiology of IUAs remains poorly understood, and current treatments often exhibit limited efficacy. We performed the single-cell RNA-sequencing (scRNA-Seq) comparison of 5 endometrial tissues, including patients with confirmed intrauterine adhesions and healthy controls(HCs). We profiled the transcriptomes of 55,308 primary human endometrial cells isolated from healthy controls and intrauterine adhesions patients at single-cell resolution. Compared with those in HCs, the number of fibroblasts derived from IUAs significantly decreased. Further analysis found that fibroblasts subcluster 3 were enriched in the IUAs, whereas opposite in HCs. GO enrichment analysis revealed that specific genes of fibroblasts subcluster 3 were markedly involved in the positive regulation of embryonic placenta development, the response to reactive oxygen species and female pregnancy, and the positive regulation of the mitotic DNA damage checkpoint and DNA damage response. In addition, the proportion of proliferating endothelial cells was significantly lower in IUAs. GO enrichment analysis revealed that the specific genes were markedly involved in the positive regulation of cell cycle arrest, the cellular response to interferon - gamma and the negative regulation of the mitotic cell cycle. According to the number of intercellular receptor-ligand pairs, we identified endothelial cells as the core cell population. Our study provides deeper insights into the endometrial microenvironment disorders that are potentially applicable to improving therapeutics for IUAs.
宫腔粘连（IUAs）是一种复杂的病症，常导致月经紊乱、不孕和产科并发症。不幸的是，IUAs的潜在病理生理学仍知之甚少，目前的治疗方法往往疗效有限。我们对5个子宫内膜组织进行了单细胞RNA测序（scRNA-Seq）比较，包括确诊为宫腔粘连的患者和健康对照（HCs）。我们以单细胞分辨率分析了从健康对照和宫腔粘连患者中分离出的55308个人类子宫内膜原代细胞的转录组。与HCs相比，来自IUAs的成纤维细胞数量显著减少。进一步分析发现，成纤维细胞亚群3在IUAs中富集，而在HCs中则相反。基因本体（GO）富集分析显示，成纤维细胞亚群3的特定基因显著参与胚胎胎盘发育的正调控、对活性氧的反应和女性妊娠，以及有丝分裂DNA损伤检查点和DNA损伤反应的正调控。此外，IUAs中增殖内皮细胞的比例显著降低。GO富集分析显示，特定基因显著参与细胞周期停滞的正调控、对干扰素-γ的细胞反应以及有丝分裂细胞周期的负调控。根据细胞间受体-配体对的数量，我们将内皮细胞确定为核心细胞群。我们的研究为子宫内膜微环境紊乱提供了更深入的见解，这可能有助于改善IUAs的治疗方法。
