Developmental Cell
Volume 57, Issue 9, 9 May 2022, Pages 1160-1176.e5
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Single-cell analysis of human testis aging and correlation with elevated body mass index

https://doi.org/10.1016/j.devcel.2022.04.004Get rights and content
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Highlights

  • A transcriptional single-cell atlas of testes from older men

  • Age-related changes in SSCs are modest

  • Age-related dysregulation of spermatogenesis and somatic cells are pronounced

  • Dysregulation correlated with BMI in older but not younger men

Summary

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.

Keywords

testis aging
male infertility
obesity
spermatogenesis
single-cell RNA sequencing
spermatogonial stem cell
testis niche
Sertoli cell
Leydig cell
peritubular myoid cell

Data and code availability

All software tools can be found online (see key resources table). The accession number for all sequencing data reported in this paper is GEO: GSE182786.

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