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

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

Paternal obesity and programming of offspring health

The physical and nutritional environment experienced by the mother prior to and during conception is imperative to the outcome of pregnancy and offspring health. In addition there is now mounting evidence that paternal exposures and conditions at the time of conception are also an important determinant of pregnancy outcome and offspring health. Specifically, male obesity is now demonstrated to have detrimental impacts on fertility and fetal development during subsequent pregnancy and can exert programming effects on the phenotype of offspring lasting up to two generations. We summarise the evidence of the effect of environmental exposures on seminal plasma and sperm, focusing on the effects of obesity, and what bearing this has for offspring both in humans and animal models. The current knowledge of what might form the molecular basis of the phenomena of paternal programming of offspring health are also reviewed with consideration given to signals from both seminal plasma and sperm.Tod Fullston, Helana S. Shehadeh, John E. Schjenken, Nicole O. McPherson, Sarah A. Robertson, Deirdre Zander-Fox, and Michelle Lan