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Conserved shifts in sperm small non-coding RNA profiles during mouse and human aging
Junchao Shi1,2,3, Xudong Zhang1,2, Chen Cai1
1Molecular Medicine Program, Division of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT, USA.
The EMBO Journal
|January 20, 2026
Summary
Sperm aging involves significant shifts in small RNA profiles, including a conserved length change in ribosomal RNA-derived small RNAs (rsRNAs) in sperm heads. This discovery offers new biomarkers for male reproductive health and aging.
Area of Science:
- Reproductive Biology
- Molecular Biology
- Genomics
Background:
- Sperm aging affects male fertility and offspring health, but molecular aging mechanisms in sperm are poorly understood.
- Identifying reliable biomarkers for sperm aging is crucial for reproductive decision-making.
Purpose of the Study:
- To profile small non-coding RNAs (sncRNAs) in aging mouse and human sperm to identify molecular determinants of sperm fitness.
- To investigate the impact of aged sperm sncRNAs on embryonic development.
Main Methods:
- Utilized PANDORA-seq to profile sperm sncRNAs, overcoming RNA modification biases.
- Analyzed sncRNA profiles across the lifespan in mouse and human sperm.
- Investigated the functional impact of aged sperm sncRNAs by transfecting them into mouse embryonic stem cells.
Main Results:
- Identified an "aging cliff" in mouse sperm RNA profiles, characterized by significant shifts in tRNA-derived small RNAs (tsRNAs) and rRNA-derived small RNAs (rsRNAs).
- Observed a conserved age-dependent length shift in sperm head rsRNAs (longer rsRNAs increase, shorter ones decrease) in both mice and humans.
- Demonstrated that aged sperm sncRNAs can induce transcriptomic changes in embryonic stem cells, affecting metabolism and neurodegeneration pathways.
Conclusions:
- Sperm sncRNA profiles undergo significant age-related changes, including a conserved rsRNA length shift in sperm heads.
- These findings provide novel insights into the molecular dynamics of sperm aging and its impact on offspring.
- The identified rsRNA length shift represents a potential biomarker for male reproductive aging.
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