Effect of Aging on the Human Myometrium at Single-Cell Resolution. Effect of Aging on the Human Myometrium at Single-Cell Resolution

The myometrial dysfunction associated with aging can prompt complications during pregnancy and labor, causing a 7.8-fold increase in maternal mortality in women over 40. Using single-cell/single-nucleus RNA sequencing and spatial transcriptomics, we constructed a cellular atlas of the aging myometrium from 186,120 cells across twenty peri- and post-menopausal women. We identified 23 myometrial cell subpopulations, including novel contractile capillary, venous capillary, immune-modulated fibroblasts, and nervous system regulatory 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 observed altered myometrial cell-to-cell communication as an aging hallmark associated with the loss of 25/229 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 women during pregnancy and labor Overall design: This series includes 20 female donors, both living and deceased, ranging from 46 to 79 years old. Donors were divided into two groups based on age: perimenopausal group (between 46 and 54 years old) and postmenopausal (> 55 years old) >>>Submitter states: Raw data are unavailable due to patient privacy concerns.<<<