Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, China.
Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, China; Shenzhen Key Laboratory for Reproductive Immunology of Peri-implantation, Clinical Research Center for Reproductive Medicine, Shenzhen Zhongshan Urology Hospital, Shenzhen, China.
J Reprod Immunol. 2023 Mar;156:103829. doi: 10.1016/j.jri.2023.103829. Epub 2023 Feb 10.
Dysfunction of decidual macrophages (dMs) are closely associated with recurrent pregnancy loss (RPL) which brings great suffering to patients. Metabolism is essential for regulating macrophage function. Identifying molecules that regulate metabolism and function of dMs is important to revealing the pathogenesis of RPL. Single-cell sequencing data of decidual immune cells from control and RPL patients were downloaded from the GSA database and converted into feature-barcode matrices by Cell Ranger. After quality control, removal of double cell and clustering of all cells, 3579 macrophages were extracted for normalisation, scaling and re-clustering. Function and metabolism analyses were performed by R packages AddMoudleScore, scMetabolism and AUCell. Metabolism clustering based on metabolism-related genes to clarify the metabolic characteristics of macrophages clusters. These results indicated that macrophage characterised by lipid metabolism were reduced in RPL and differential expression genes analysis found that HSP70 was significantly decreased in the RPL group. Furthermore, immunofluorescence staining demonstrated that HSP70 was significantly downregulated in dMs of RPL patients compared to controls. In conclusion, HSP70 may maintain normal pregnancy by regulating lipid metabolism of dMs. This study provides new insights into the molecular mechanisms regulating the function of dMs and provides a theoretical basis for the development of new therapies for RPL.
蜕膜巨噬细胞（dMs）功能障碍与复发性妊娠丢失（RPL）密切相关，给患者带来极大痛苦。代谢对于调节巨噬细胞功能至关重要。鉴定调节 dMs 代谢和功能的分子对于揭示 RPL 的发病机制很重要。从 GSA 数据库下载了对照和 RPL 患者的蜕膜免疫细胞的单细胞测序数据，并通过 Cell Ranger 转换为特征条形码矩阵。经过质量控制、去除双细胞和所有细胞聚类后，提取了 3579 个巨噬细胞进行归一化、缩放和重新聚类。通过 R 包 AddMoudleScore、scMetabolism 和 AUCell 进行功能和代谢分析。基于代谢相关基因的代谢聚类，以阐明巨噬细胞簇的代谢特征。这些结果表明，RPL 中脂质代谢相关的巨噬细胞特征减少，差异表达基因分析发现 HSP70 在 RPL 组中显著减少。此外，免疫荧光染色表明，与对照组相比，RPL 患者的 dMs 中 HSP70 明显下调。总之，HSP70 可能通过调节 dMs 的脂质代谢来维持正常妊娠。这项研究为调节 dMs 功能的分子机制提供了新的见解，并为 RPL 的新疗法的发展提供了理论依据。
