A single-cell transcriptomic landscape of mouse testicular aging

Introduction: Advanced paternal age of reproduction is an increasing trend, especially in developed coun-tries and areas. This trend results in elevated risks of adverse reproductive outcomes such as reduced fer-tility rates, increased pregnancy loss, and poor childhood health. Yet, a systematic profiling of aging -associated molecular and cellular alterations in testicular tissue is still missing. Objectives: We aimed to dissect aging-associated molecular characteristics in testes of mice. Methods: Single-cell transcriptomic sequencing and analysis were conducted in testes of young (2 months old) and old mice (24 months old). Immunofluorescences and immunochemistry were used to character-ize aging-associated phenotypes and verify single cell sequence results. Results: Here, we constructed the first single-cell transcriptomic atlases of testes of young and old mice. In-depth dissection of aging-dependent transcriptional alterations in specific cell types revealed multiple dysregulated biological processes such as increased 'senescence-associated secretory phenotype' and 'in-flammation', which were major aging-associated characteristics. Further analysis of aging-related differ-entially expressed genes uncovered a disrupted balance of undifferentiated and differentiated spermatogonia stem cells in spermatogonia, indicative of a potential role of spermatogonia stem cells in aging-associated subfertility. Importantly, for the first time, our results identified an increased subtype of aging-specific macrophages, which may contribute to a hostile proinflammatory microenvironment during testicular aging. Conclusion: Taken together, our findings depict the distinct single-cell transcriptional features of the aged mouse testes and provide enormous resources for a comprehensive understanding of the cell-type -specific molecular mechanisms underlying mouse testicular aging, which may shed light on developing novel potential diagnostic biomarkers and therapeutic targets for age-associated male subfertility. (c) 2023 The Authors. Published by Elsevier B.V. on behalf of Cairo University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

This study focuses on the reproductive issues of advanced paternal age and analyzes the molecular and cellular changes associated with aging in the testes of mice. The study discovers various aging-related biological processes and identifies an increased subtype of aging-specific macrophages that contribute to a proinflammatory environment during testicular aging.