Effect of aging on the human myometrium at single-cell resolution

Paula Punzon-Jimenez, Alba Machado-Lopez, Raul Perez-Moraga, Jaime Llera-Oyola, Daniela Grases, Marta Galvez-Viedma, Mustafa Sibai, Elena Satorres-Perez, Susana Lopez-Agullo, Rafael Badenes, Carolina Ferrer-Gomez, Eduard Porta-Pardo, Beatriz Roson, Carlos Simon () and Aymara Mas ()
Additional contact information
Paula Punzon-Jimenez: Carlos Simon Foundation
Alba Machado-Lopez: Carlos Simon Foundation
Raul Perez-Moraga: Carlos Simon Foundation
Jaime Llera-Oyola: Carlos Simon Foundation
Daniela Grases: Josep Carreras Leukaemia Research Institute (IJC)
Marta Galvez-Viedma: Carlos Simon Foundation
Mustafa Sibai: Josep Carreras Leukaemia Research Institute (IJC)
Elena Satorres-Perez: Hospital Universitario y Politécnico La Fe
Susana Lopez-Agullo: Hospital Universitario y Politécnico La Fe
Rafael Badenes: University of Valencia
Carolina Ferrer-Gomez: Hospital General Universitario de Valencia
Eduard Porta-Pardo: Josep Carreras Leukaemia Research Institute (IJC)
Beatriz Roson: Carlos Simon Foundation
Carlos Simon: Carlos Simon Foundation
Aymara Mas: Carlos Simon Foundation

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-45143-z

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