Characterisation of mouse epididymosomes reveals a complex profile of microRNAs and a potential mechanism for modification of the sperm epigenome.

Jackson N Reilly,Andrew L Eamens,Amanda L Anderson,Bettina P Mihalas,Eileen A Mclaughlin,Kate Hutcheon,Janet E Holt,Kiralee Church,Brett Nixon,Simone J Stanger,Sonika Tyagi

doi:10.1038/srep31794

Abstract

Recent evidence has shown that the sperm epigenome is vulnerable to dynamic modifications arising from a variety of paternal environment exposures and that this legacy can serve as an important determinant of intergenerational inheritance. It has been postulated that such exchange is communicated to maturing spermatozoa via the transfer of small non-protein-coding RNAs (sRNAs) in a mechanism mediated by epididymosomes; small membrane bound vesicles released by the soma of the male reproductive tract (epididymis). Here we confirm that mouse epididymosomes encapsulate an impressive cargo of >350 microRNAs (miRNAs), a developmentally important sRNA class, the majority (~60%) of which are also represented by the miRNA signature of spermatozoa. This includes >50 miRNAs that were found exclusively in epididymal sperm and epididymosomes, but not in the surrounding soma. We also documented substantial changes in the epididymosome miRNA cargo, including significant fold changes in almost half of the miRNAs along the length of the epididymis. Finally, we provide the first direct evidence for the transfer of several prominent miRNA species between mouse epididymosomes and spermatozoa to afford novel insight into a mechanism of intercellular communication by which the sRNA payload of sperm can be selectively modified during their post-testicular maturation.

Highlights

Similar to the exosome population documented in other somatic tissues and bodily fluids, epididymosomes are able to relay a complex macromolecular cargo to recipient cells[9,10,11]
This study extends on the previous work that has identified the miRNA class of small non-protein-coding RNAs (sRNAs) as an additional and potentially developmentally important tier of regulation in the male reproductive tract[11,22,26,28,29,30]
Through development of a tractable protocol for the isolation of mouse epididymosomes, here we provide novel insight into the complexity of the segment specific miRNA profiles of these extracellular vesicles as well as exploring their capacity to deliver this important regulatory cargo to maturing spermatozoa

Summary

Introduction

Similar to the exosome population documented in other somatic tissues and bodily fluids, epididymosomes are able to relay a complex macromolecular cargo to recipient cells[9,10,11]. A similar number of differentially accumulating miRNAs were identified among the 342 miRNAs detected in corpus and cauda epididymosome fractions (13% up- and 9% down-regulated; Fig. 2b and Supplementary Table S2).

Results

Conclusion