生物
输卵管
纤维化
子宫
细胞外基质
炎症
蜕膜化
卵巢
发情周期
衰老
细胞生物学
内分泌学
内科学
免疫学
医学
作者
Ivana Winkler,Alexander Tolkachov,Fritjof Lammers,Perrine Lacour,Klaudija Daugėlaitė,Nina Schneider,Marie-Luise Koch,Jasper Panten,Florian Grünschläger,Tanja Poth,Bianca Machado de Ávila,Augusto Schneider,Simon Haas,Duncan T. Odom,Ângela Gonçalves
出处
期刊:Cell
[Elsevier]
日期:2024-02-01
卷期号:187 (4): 981-998.e25
标识
DOI:10.1016/j.cell.2024.01.021
摘要
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.
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