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

Author:

Punzón-Jiménez PORCID,Machado-Lopez AORCID,Pérez-Moraga RORCID,Llera-Oyola J,Grases D,Galvez-Viedma M,AlSibai M,Satorres E,Badenes RORCID,Ferrer C,Porta-Pardo E,Roson BORCID,Simón C,Mas AORCID

Abstract

AbstractThe 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.

Publisher

Cold Spring Harbor Laboratory

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