TY  - JOUR
AU  - Winkler, Ivana
AU  - Tolkachov, Alexander
AU  - Lammers, Fritjof
AU  - Lacour, Perrine
AU  - Daugelaite, Klaudija
AU  - Schneider, Nina
AU  - Koch, Marie-Luise
AU  - Panten, Jasper
AU  - Grünschläger, Florian
AU  - Poth, Tanja
AU  - Ávila, Bianca Machado de
AU  - Schneider, Augusto
AU  - Haas, Simon
AU  - Odom, Duncan T
AU  - Gonçalves, Ângela
TI  - The cycling and aging mouse female reproductive tract at single-cell resolution.
JO  - Cell
VL  - 187
IS  - 4
SN  - 0092-8674
CY  - New York, NY
PB  - Elsevier
M1  - DKFZ-2024-00296
SP  - 981-998.e25
PY  - 2024
N1  - DKFZ–ZMBH Alliance / 2024 Feb 15;187(4):981-998.e25 / #EA:B210#LA:B210#
AB  - 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.
KW  - aging (Other)
KW  - cervix (Other)
KW  - fibrosis (Other)
KW  - inflammation (Other)
KW  - ovary (Other)
KW  - oviduct (Other)
KW  - single cell (Other)
KW  - spatial (Other)
KW  - uterus (Other)
KW  - vagina (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:38325365
DO  - DOI:10.1016/j.cell.2024.01.021
UR  - https://inrepo02.dkfz.de/record/287653
ER  -