Du Yue, Shuai Ruzhen, Luo Sang, Jin Yiran, Xu Fengjuan, Zhang Jingyi, Liu Dan, Feng Limin
Department of Obstetrics, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, China.
Department of Obstetrics and Gynecology, Gansu Provincial Hospital, Lanzhou, Gansu, 730000, China.
Biol Direct. 2024 Dec 26;19(1):142. doi: 10.1186/s13062-024-00583-x.
Intrauterine adhesion (IUA) is a common cause of clinically refractory infertility, and there exists significant heterogeneity in the treatment outcomes among IUA patients with the similar severity after transcervical resection of adhesion(TCRA). The underlying mechanism of different treatment outcomes occur remains elusive, and the precise contribution of various cell subtypes in this process remains uncertain.
Here, we performed single-cell transcriptome sequencing on 10 human endometrial samples to establish a single-cell atlas differences between patients who responded to estrogen therapy and those who did not. The results showed increased infiltration of immune cells such as monocyte macrophages, T cells, and natural killer (NK) cells in patients who did not respond to estrogen therapy. Our findings indicate that distinct fibroblast subsets are implicated in the modulation of the Wnt, Hippo, and Hedgehog signaling pathways, as evidenced by functional enrichment analyses. This may have implications for the therapeutic efficacy in patients with IUA. Furthermore, we delineated the markers and transcriptional status of different macrophage subsets and identified two cell clusters, CXCL10high and CCL4L2high macrophage subsets, which are intimately associated with inflammation and fibrosis. The state of fibrosis and inflammatory response in human endometrial tissues with disparate treatment outcomes is revealed, and providing evidence to clarify the underlying determinants of sensitivity to estrogen therapy.
We described the transcriptional status of different cell subtypes in the two groups of patients, providing new ideas for exploring the molecular mechanism of the difference in the effectiveness of estrogen therapy in patients, and providing theoretical basis for providing precise and individualized treatment plans for IUA patients.
宫腔粘连（IUA）是临床难治性不孕症的常见原因，在宫腔镜粘连切除术（TCRA）后，严重程度相似的IUA患者的治疗效果存在显著异质性。不同治疗效果产生的潜在机制仍不清楚，在此过程中各种细胞亚型的确切作用也不确定。
在此，我们对10例人类子宫内膜样本进行了单细胞转录组测序，以建立雌激素治疗反应者和无反应者之间的单细胞图谱差异。结果显示，雌激素治疗无反应患者中单核巨噬细胞、T细胞和自然杀伤（NK）细胞等免疫细胞浸润增加。我们的研究结果表明，不同的成纤维细胞亚群参与了Wnt、Hippo和Hedgehog信号通路的调节，功能富集分析证明了这一点。这可能对IUA患者的治疗效果有影响。此外，我们描绘了不同巨噬细胞亚群的标志物和转录状态，鉴定出两个细胞簇，即CXCL10高表达和CCL4L2高表达巨噬细胞亚群，它们与炎症和纤维化密切相关。揭示了不同治疗结果的人类子宫内膜组织中的纤维化和炎症反应状态，为阐明雌激素治疗敏感性的潜在决定因素提供了证据。
我们描述了两组患者中不同细胞亚型的转录状态，为探索患者雌激素治疗效果差异的分子机制提供了新思路，为IUA患者提供精准个体化治疗方案提供了理论依据。
