Carlos Simon Foundation, Valencia, Spain.
Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain.
Nat Commun. 2024 Jan 31;15(1):945. doi: 10.1038/s41467-024-45143-z.
Age-associated myometrial dysfunction can prompt complications during pregnancy and labor, which is one of the factors contributing to the 7.8-fold increase in maternal mortality in women over 40. Using single-cell/single-nucleus RNA sequencing and spatial transcriptomics, we have constructed a cellular atlas of the aging myometrium from 186,120 cells across twenty perimenopausal and postmenopausal women. We identify 23 myometrial cell subpopulations, including contractile and venous capillary cells as well as immune-modulated fibroblasts. Myometrial aging leads to fewer contractile capillary cells, a reduced level of ion channel expression in smooth muscle cells, and impaired gene expression in endothelial, smooth muscle, fibroblast, perivascular, and immune cells. We observe altered myometrial cell-to-cell communication as an aging hallmark, which associated with the loss of 25 signaling pathways, including those related to angiogenesis, tissue repair, contractility, immunity, and nervous system regulation. These insights may contribute to a better understanding of the complications faced by older individuals during pregnancy and labor.
与年龄相关的子宫肌功能障碍会在妊娠和分娩期间引发并发症，这是导致 40 岁以上女性产妇死亡率增加 7.8 倍的因素之一。通过单细胞/单细胞核 RNA 测序和空间转录组学，我们从 20 名围绝经期和绝经后女性的 186120 个细胞中构建了衰老子宫肌的细胞图谱。我们鉴定出 23 种子宫肌细胞亚群，包括收缩性和静脉毛细血管细胞以及免疫调节成纤维细胞。子宫肌衰老导致收缩性毛细血管细胞减少，平滑肌细胞中离子通道表达水平降低，以及内皮细胞、平滑肌细胞、成纤维细胞、血管周细胞和免疫细胞的基因表达受损。我们观察到衰老的标志是子宫肌细胞间通讯的改变，这与 25 条信号通路的丧失有关，包括与血管生成、组织修复、收缩性、免疫和神经系统调节相关的信号通路。这些见解可能有助于更好地理解老年人在妊娠和分娩期间面临的并发症。
