title: Characterisation of mouse epididymosomes reveals a complex profile of microRNAs and a potential mechanism for modification of the sperm epigenome.
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.
authors.affiliation: Priority Research Centre for Reproduction, School of Environmental and Life Sciences, Discipline of Biological Sciences, University of Newcastle, Callaghan, New South Wales 2308, Australia.
authors.forename: Jackson N
authors.initials: JN
authors.lastname: Reilly
authors.affiliation: Priority Research Centre for Reproduction, School of Environmental and Life Sciences, Discipline of Biological Sciences, University of Newcastle, Callaghan, New South Wales 2308, Australia.|School of Biological Sciences, University of Auckland, Auckland 1142, New Zealand.
authors.forename: Eileen A
authors.initials: EA
authors.lastname: McLaughlin
authors.affiliation: Priority Research Centre for Reproduction, School of Environmental and Life Sciences, Discipline of Biological Sciences, University of Newcastle, Callaghan, New South Wales 2308, Australia.
authors.forename: Simone J
authors.initials: SJ
authors.lastname: Stanger
authors.affiliation: Priority Research Centre for Reproduction, School of Environmental and Life Sciences, Discipline of Biological Sciences, University of Newcastle, Callaghan, New South Wales 2308, Australia.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Anderson
authors.affiliation: School of Environmental and Life Sciences, Discipline of Biological Sciences, University of Newcastle, Callaghan, New South Wales 2308, Australia.
authors.forename: Kate
authors.initials: K
authors.lastname: Hutcheon
authors.affiliation: Priority Research Centre for Reproduction, School of Environmental and Life Sciences, Discipline of Biological Sciences, University of Newcastle, Callaghan, New South Wales 2308, Australia.
authors.forename: Kiralee
authors.initials: K
authors.lastname: Church
authors.affiliation: Priority Research Centre for Reproduction, School of Environmental and Life Sciences, Discipline of Biological Sciences, University of Newcastle, Callaghan, New South Wales 2308, Australia.
authors.forename: Bettina P
authors.initials: BP
authors.lastname: Mihalas
authors.affiliation: Australian Genome Research Facility Ltd, The Walter and Eliza Hall Institute, Parkville, Victoria 3052, Australia.
authors.forename: Sonika
authors.initials: S
authors.lastname: Tyagi
authors.affiliation: School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, New South Wales 2308, Australia.
authors.forename: Janet E
authors.initials: JE
authors.lastname: Holt
authors.affiliation: School of Environmental and Life Sciences, Discipline of Biological Sciences, University of Newcastle, Callaghan, New South Wales 2308, Australia.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Eamens
authors.affiliation: Priority Research Centre for Reproduction, School of Environmental and Life Sciences, Discipline of Biological Sciences, University of Newcastle, Callaghan, New South Wales 2308, Australia.
authors.forename: Brett
authors.initials: B
authors.lastname: Nixon
mesh_terms: D000818:Animals; D016000:Cluster Analysis; D019295:Computational Biology; D004822:Epididymis / Q000378:metabolism*; D005837:Genitalia, Male / Q000378:metabolism; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D012984:Software; D013079:Sperm Maturation; D013094:Spermatozoa / Q000378:metabolism*
chemical_list: D035683:MicroRNAs