Single-cell analysis of human testis aging and correlation with elevated body mass index.

Autor:	Nie X; Division of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT 84112, USA; Howard Hughes Medical Institute, Department of Oncological Sciences and Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84112, USA., Munyoki SK; Department of Obstetrics, Gynecology and Reproductive Sciences and Magee-Womens Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA., Sukhwani M; Department of Obstetrics, Gynecology and Reproductive Sciences and Magee-Womens Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA., Schmid N; Biomedical Center Munich (BMC), Cell Biology, Anatomy III, Ludwig-Maximilians-University (LMU), Grosshaderner Strasse 9, Planegg, Munich, 82152, Germany., Missel A; Biomedical Center Munich (BMC), Cell Biology, Anatomy III, Ludwig-Maximilians-University (LMU), Grosshaderner Strasse 9, Planegg, Munich, 82152, Germany., Emery BR; Division of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT 84112, USA., DonorConnect; DonorConnect, Murry, UT 84107, USA., Stukenborg JB; NORDFERTIL Research Laboratory Stockholm, Childhood Cancer Research Unit, Bioclinicum J9:30, Department of Women's and Children's Health, Karolinska Institutet, and Karolinska University Hospital, Solna 17164, Sweden., Mayerhofer A; Biomedical Center Munich (BMC), Cell Biology, Anatomy III, Ludwig-Maximilians-University (LMU), Grosshaderner Strasse 9, Planegg, Munich, 82152, Germany., Orwig KE; Department of Obstetrics, Gynecology and Reproductive Sciences and Magee-Womens Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA., Aston KI; Division of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT 84112, USA., Hotaling JM; Division of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT 84112, USA., Cairns BR; Howard Hughes Medical Institute, Department of Oncological Sciences and Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84112, USA. Electronic address: brad.cairns@hci.utah.edu., Guo J; Division of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT 84112, USA; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: jingtao.guo@ioz.ac.cn.
Jazyk:	angličtina
Zdroj:	Developmental cell [Dev Cell] 2022 May 09; Vol. 57 (9), pp. 1160-1176.e5. Date of Electronic Publication: 2022 May 02.
DOI:	10.1016/j.devcel.2022.04.004
Abstrakt:	Aging men display reduced reproductive health; however, testis aging is poorly understood at the molecular and genomic levels. Here, we utilized single-cell RNA-seq to profile over 44,000 cells from both young and older men and examined age-related changes in germline development and in the testicular somatic cells. Age-related changes in spermatogonial stem cells appeared modest, whereas age-related dysregulation of spermatogenesis and somatic cells ranged from moderate to severe. Altered pathways included signaling and inflammation in multiple cell types, metabolic signaling in Sertoli cells, hedgehog signaling and testosterone production in Leydig cells, cell death and growth in testicular peritubular cells, and possible developmental regression in both Leydig and peritubular cells. Remarkably, the extent of dysregulation correlated with body mass index in older but not in younger men. Collectively, we reveal candidate molecular mechanisms underlying the complex testicular changes conferred by aging and their possible exacerbation by concurrent chronic conditions such as obesity. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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