The contribution of epididymosomes to the sperm small RNA profile

Abstract

It is now well established that mature spermatozoa harbour a rich and diverse profile of small non-protein-coding regulatory RNAs (sRNAs). There is also growing appreciation that this sRNA profile displays considerable plasticity, being altered in response to paternal exposure to a variety of environmental stressors. Coupled with evidence that upon delivery to the oocyte at the moment of fertilisation, sperm-borne sRNAs are able to influence both early embryonic development and the subsequent health of the offspring, there is now interest in both the timing and degree of change in the composition of the sRNA cargo of sperm. Models in which such epigenetic changes are linked to the spermatogenic cycle are seemingly incompatible with the lack of overt phenotypic changes in the spermatozoa of affected males. Rather, there is mounting consensus that such changes are imposed on sperm during their transit and storage within the epididymis, a protracted developmental window that takes place over several weeks. Notably, since spermatozoa are rendered transcriptionally and translationally silent during their development in the testes, it is most likely that the epididymis-documented alterations to the sperm sRNA profile are driven extrinsically, with a leading candidate being epididymosomes: small membrane enclosed extracellular vesicles that encapsulate a complex macromolecular cargo of proteins and RNAs, including the sRNAs. Here, we review the role of epididymosome–sperm communication in contributing to the establishment of the sperm sRNA profile during their epididymal transit.

Differential gene expression profiles of human efferent ducts and proximal epididymis

“…After leaving the testis, mammalian spermatozoa must transit the epididymis in order to acquire their forward motility properties and fertilizing ability . The epididymis is also responsible for sperm storage, and emerging evidence supports the concept that this male reproductive tract organ is the theater of sperm epigenome modifications involved in post‐fertilization events . Whereas the epididymis is part of the male reproductive tract of all vertebrate species practicing internal fertilization, the anatomy of this organ shows great phylogenetic variability even within the mammalian phylum .…”

The landscape of mouse epididymal cells defined by the single-cell RNA-Seq

“…Region specific gene expression of epididymis in the mouse and human was also studied by microarray analysis(Johnston et al, 2005; Zhang et al, 2006). On the other hand, it was plausible that the epididymosome was contributed to the sperm modifications during the sperm transient in epididymis (Sharma et al, 2018; Trigg et al, 2019). Recently, James et al demonstrated the expression profiles of segment-specific human epididymal epithelial cells (Browne et al, 2016).…”

Seminal Plasma Transcriptome and Proteome: Towards a Molecular Approach in the Diagnosis of Idiopathic Male Infertility

“…Particularly, epididymosomes are extracellular vesicles released by the epididymal epithelium, which encapsulate a macromolecular complex made up of proteins (required to avoid RNA degradation) and RNAs. During the sperm transit into the epididymis, epididymosomes interact with spermatozoa by modulating their RNA profile [11]. In more detail, while miRNAs are the most represented class of sRNA in the caput epididymis, tRFs are more abundantly found in the cauda [16,17].…”

“…The seminal plasma (SP) is made-up of secretions arising from the male accessory glands, namely epididymis, seminal vesicles, and prostate. The SP is not only a medium for sperm transport, since it can modulate the female reproductive environment and immunity [9] to allow the acquisition of sperm competence [10] to influence sperm RNA content, and even embryo development, as transcriptome studies reveal [11]. In recent years, thousands of specific transcripts and proteins have been found in human seminal plasma (SP).…”