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The cycling and aging mouse female reproductive tract at single-cell resolution

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Item Type:Article
Title:The cycling and aging mouse female reproductive tract at single-cell resolution
Creators Name:Winkler, I. and Tolkachov, A. and Lammers, F. and Lacour, P. and Daugelaite, K. and Schneider, N. and Koch, M.L. and Panten, J. and Grünschläger, F. and Poth, T. and Ávila, B.M.d. and Schneider, A. and Haas, S. and Odom, D.T. and Gonçalves, Â.
Abstract:The female reproductive tract (FRT) undergoes extensive remodeling during reproductive cycling. This recurrent remodeling and how it shapes organ-specific aging remains poorly explored. Using single-cell and spatial transcriptomics, we systematically characterized morphological and gene expression changes occurring in ovary, oviduct, uterus, cervix, and vagina at each phase of the mouse estrous cycle, during decidualization, and into aging. These analyses reveal that fibroblasts play central-and highly organ-specific-roles in FRT remodeling by orchestrating extracellular matrix (ECM) reorganization and inflammation. Our results suggest a model wherein recurrent FRT remodeling over reproductive lifespan drives the gradual, age-related development of fibrosis and chronic inflammation. This hypothesis was directly tested using chemical ablation of cycling, which reduced fibrotic accumulation during aging. Our atlas provides extensive detail into how estrus, pregnancy, and aging shape the organs of the female reproductive tract and reveals the unexpected cost of the recurrent remodeling required for reproduction.
Keywords:Ovary, Oviduct, Uterus, Cervix, Vagina, Inflammation, Fibrosis, Spatial, Single Cell, Animals, Mice
Publisher:Cell Press
Page Range:981-998
Date:15 February 2024
Official Publication:https://doi.org/10.1016/j.cell.2024.01.021
PubMed:View item in PubMed

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