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

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 c...

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Main Authors: Winkler, Ivana (Author) , Tolkachov, Alexander (Author) , Lammers, Fritjof Paul (Author) , Lacour, Perrine (Author) , Daugėlaitė, Klaudija (Author) , Schneider, Nina (Author) , Koch, Marie-Luise (Author) , Panten, Jasper (Author) , Grünschläger, Florian (Author) , Poth, Tanja (Author) , Ávila, Bianca Machado de (Author) , Schneider, Augusto (Author) , Haas, Simon (Author) , Odom, Duncan T. (Author) , Gonçalves, Ângela (Author)
Format: Article (Journal)
Language:English
Published: 15 February 2024,
In: Cell
Year: 2024, Volume: 187, Issue: 4, Pages: 981-998.e25
ISSN:1097-4172
DOI:10.1016/j.cell.2024.01.021
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.cell.2024.01.021
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S0092867424000588
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Author Notes:Ivana Winkler, Alexander Tolkachov, Fritjof Lammers, Perrine Lacour, Klaudija Daugelaite, Nina Schneider, Marie-Luise Koch, Jasper Panten, Florian Grünschläger, Tanja Poth, Bianca Machado de Ávila, Augusto Schneider, Simon Haas, Duncan T. Odom, and Ângela Gonçalves
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Summary: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.
Item Description:Online verfügbar: 6. Februar 2024, Artikelversion: 15. Februar 2024
Gesehen am 22.08.2024
Physical Description:Online Resource
ISSN:1097-4172
DOI:10.1016/j.cell.2024.01.021

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