The Small Non-Coding RNA Profile of Human and Mouse Sperm

Small non-coding RNAs constitute a dynamic epigenetic layer in mature spermatozoa that can exert transgenerational regulatory functions. Here, we review recent advances in the field of small RNAs in spermatozoa, how their profiles change in response to lifestyle or environmental factors, and their impact on offsprings' physiology. The profile of these RNAs changes dramatically during spermatozoa maturation. The majority of intracellular small RNAs during early spermatogenesis are miRNAs and piRNAs, but, in mature spermatozoa, tRNA- and rRNA-derived fragments (tRFs and rRFs, respectively) are the predominant forms, primarily delivered from the epididymis via extracellular vesicles. Diet, exercise, and environmental exposures have a direct effect on small RNA levels in spermatozoa, and this differential abundance can reprogram the development of the embryo. Offsprings of fathers with different lifestyles can have different phenotypes, including altered metabolism or behavior. Therefore, small RNAs in spermatozoa are emerging as an important epigenetic layer in development and transgenerational inheritance.