image: RNA modification abundance in different RNA fractions across distinct spermatogenic cell types and sperm from different epididymal segments
Credit: ©Science China Press
RNA modifications are chemical marks on RNA molecules that can influence RNA stability, processing and function. Although several of these marks have been linked to spermatogenesis and male fertility, how they change as germ cells develop into mature sperm has remained unclear.
To address this, the researchers used a liquid chromatography-tandem mass spectrometry-based platform to quantify 27 RNA modifications in total RNA, tRNA-enriched RNA and small RNA. They analysed developing mouse testes, isolated spermatogenic cells and sperm collected from different regions of the epididymis.
Together, these findings trace a molecular journey of sperm development. RNA modification patterns changed across testis development, with tRNA-enriched RNA showing especially strong stage-specific signatures. As sperm moved through the epididymis — where they acquire fertilization competence — their RNA modification landscape was further remodelled, showing that the sperm RNA code continues to change after leaving the testis.
The study also found that this programme is sensitive to metabolic stress. In a typeⅡ diabetes mouse model, sperm RNA modification profiles were markedly altered during epididymal maturation. Diabetes changed not only the levels of individual RNA marks, but also the correlation networks between them.
These results suggest that sperm maturation involves a carefully coordinated reshaping of epigenetic information, and that paternal metabolic disease can disrupt this process. The study provides a framework for exploring how sperm RNA modifications may influence male fertility and potentially offspring health.
The authors note that the current approach measures overall modification abundance rather than pinpointing specific RNA sites. Future work combining transcriptome sequencing with site-specific RNA modification profiling will be needed to reveal exactly where these marks occur and how they regulate sperm function.
Journal
Science China Life Sciences
Method of Research
Experimental study