Journal Article

DKFZ-2024-00296

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The cycling and aging mouse female reproductive tract at single-cell resolution.

Winkler, I. (First author)DKFZ* ; Tolkachov, A.DKFZ* ; Lammers, F.DKFZ* ; Lacour, P.DKFZ* ; Daugelaite, K.DKFZ* ; Schneider, N.DKFZ* ; Koch, M.-L.DKFZ* ; Panten, J.DKFZ* ; Grünschläger, F.DKFZ* ; Poth, T. ; Ávila, B. M. d. ; Schneider, A. ; Haas, S.DKFZ* ; Odom, D. T.DKFZ* ; Gonçalves, Â. (Last author)DKFZ*

2024
Elsevier New York, NY

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Please use a persistent id in citations: doi:10.1016/j.cell.2024.01.021

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.

Keyword(s): aging ; cervix ; fibrosis ; inflammation ; ovary ; oviduct ; single cell ; spatial ; uterus ; vagina

Note: DKFZ–ZMBH Alliance / 2024 Feb 15;187(4):981-998.e25 / #EA:B210#LA:B210#

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Contributing Institute(s):

1. B210 NWG Somatische Evolution und Früherkennung (B210)
2. B270 Regulatorische Genomik und Evolution von Tumoren (B270)
3. B260 Bioinformatik der Genomik und Systemgenetik (B260)
4. A010 Stammzellen und Krebs (A010)
5. DKTK HD zentral (HD01)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2024

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 60 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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