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

被引：40

作者：

Winkler, Ivana ^{[1
]}

Tolkachov, Alexander ^{[2
,15
]}

Lammers, Fritjof ^{[2
]}

Lacour, Perrine ^{[1
,3
]}

Daugelaite, Klaudija ^{[2
,3
]}

Schneider, Nina ^{[1
]}

Koch, Marie-Luise ^{[2
]}

Panten, Jasper ^{[2
,4
]}

Gruenschlaeger, Florian ^{[2
,3
,5
,6
,7
]}

Poth, Tanja ^{[8
]}

de Avila, Bianca Machado ^{[9
]}

Schneider, Augusto ^{[9
]}

Haas, Simon ^{[5
,6
,10
,11
,12
,13
]}

Odom, Duncan T. ^{[2
,14
]}

Goncalves, Angela ^{[1
]}

机构：

[1] German Canc Res Ctr, Div Somat Evolut & Early Detect, D-69120 Heidelberg, Germany

[2] German Canc Res Ctr, Div Regulatory Genom & Canc Evolut, D-69120 Heidelberg, Germany

[3] Heidelberg Univ, Fac Biosci, D-69117 Heidelberg, Germany

[4] German Canc Res Ctr, Div Computat Genom & Systems Genet, D-69120 Heidelberg, Germany

[5] German Canc Res Ctr, D-69120 Heidelberg, Germany

[6] DKFZ ZMBH Alliance, Div Stem Cells & Canc, D-69120 Heidelberg, Germany

[7] Heidelberg Inst Stem Cell Technol & Expt Med HISTE, D-69120 Heidelberg, Germany

[8] Univ Hosp Heidelberg, Inst Pathol, CMCP Ctr Model Syst & Comparat Pathol, D-69120 Heidelberg, Germany

[9] Univ Fed Pelotas, Fac Nutr, BR-96010610 Pelotas, RS, Brazil

[10] Charite Univ med Berlin, Berlin Inst Hlth BIH, D-10117 Berlin, Germany

[11] Helmholtz Assoc, Berlin Inst Med Syst Biol, Max Delbruck Ctr Mol Med, D-10115 Berlin, Germany

[12] German Canc Consortium DKTK, D-69120 Heidelberg, Germany

[13] Charite Univ med Berlin, Dept Hematol Oncol & Canc Immunol, D-10115 Berlin, Germany

[14] Univ Cambridge, Canc Res UK Cambridge Inst, Cambridge, England

[15] Heidelberg Univ Hosp, Dept Cardiol Angiol & Pneumol Internal Med 3, D-69120 Heidelberg, Germany

来源：

CELL | 2024年 / 187卷 / 04期

基金：

欧洲研究理事会;

关键词：

HUMAN ENDOMETRIUM; ESTROUS-CYCLE; R-PACKAGE; MENSTRUAL-CYCLE; ALPHA; MICE; RNA; DECIDUALIZATION; COMMUNICATION; PROGESTERONE;

D O I：

10.1016/j.cell.2024.01.021

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

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, agerelated 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.

引用

页码：981 / 998.e25

页数：44

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