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

Fecha de publicación: 31/01/2024 Fecha Ahead of Print: 31/01/2024

Autores de IIS La Fe

• Susana López Agulló

  Autor

• Beatriz Rosón Burgo

  Autor

• Carlos Simon Valles

  Autor

• Aymara Mas Perucho

  Autor

Participantes ajenos a IIS La Fe

• Punzon-Jimenez, Paula
• Machado-Lopez, Alba
• Perez-Moraga, Raul
• Llera-Oyola, Jaime
• Grases, Daniela
• Galvez-Viedma, Marta
• Sibai, Mustafa
• Satorres-Perez, Elena
• Badenes, Rafael
• Ferrer-Gomez, Carolina
• Porta-Pardo, Eduard

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.

© 2024. The Author(s).

Keywords

• UTERINE JUNCTIONAL ZONE; DYSFUNCTION; SENESCENCE; REVEALS; SYSTEM; HEALTH; AGE