Epididymosomes Convey Different Repertoires of MicroRNAs Throughout the Bovine Epididymis1

Abstract

Epididymosomes are small membrane vesicles that are secreted by epididymal epithelial cells and are involved in posttesticular sperm maturation. Although their role in protein transfer to the sperm membrane is well documented, we report their capacity to transport microRNAs (miRNAs), which are potent regulators of posttranscriptional gene expression. Using a microperfusion technique combined with a global microarray approach, we demonstrated that epididymosomes from two discrete bovine epididymal regions (caput and cauda) possess distinct miRNA signatures. In addition, we also established that miRNA repertoires contained within epididymosomes differ from those of their parent epithelial cells, suggesting that miRNA populations released from the cells may be selectively sorted. Binding of DilC12-labeled epididymosomes to primary cultured epididymal cells was measured by flow cytometry, and the results indicated that epididymosomes from the median caput and their miRNA content may be incorporated into distal caput epithelial cells. Overall, these findings reveal that distinct miRNA repertoires are released into the intraluminal fluid in a region-specific manner and could be involved in a novel mechanism of intercellular communication throughout the epididymis via epididymosomes.

tRNA fragments: novel players in intergenerational inheritance

“…They incubated caput sperm with isolated epididymosomes and performed comparative sequencing of the sperm before and after the incubation. Their observations are consistent with previous bovine studies that describe the convey of small RNA by epididymosomes to developing sperm cells [10].…”

Transgenerational epigenetic programming via sperm microRNA recapitulates effects of paternal stress

“…Rodent models examining paternal transmission have identified epigenetic signatures in mature sperm as possible substrates of transgenerational programming, namely patterns of retained histone modifications, DNA methylation, and/or populations of small noncoding RNAs (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). RNA populations are of primary interest, as they may be altered through intercellular communication via epididymosomes even in transcriptionally inert mature sperm, where DNA condensation impedes other epigenetic change (22)(23)(24). Studies in which manipulation of total RNA content in postfertilization zygotes reproduced aspects of a paternally transmitted phenotype highlight the critical importance of RNA as a germ cell epigenetic mark and support the potential role of small RNAs, including microRNAs (miRs), in trait transmission (20,25).…”

Cell-secreted vesicles containing microRNAs as regulators of gamete maturation

“…Additionally, miR-145, miR-143, miR-214 and miR-199 were present in higher amounts in epididymosomes from caput, while miR-654, miR-1224 and miR-395 are higher in epididymosomes collected from the cauda region (Belleannée et al 2013). Moreover, epididymosomes secreted within the epididymis intraluminal environment can be taken up by surrounding epithelial cells possibly regulating transcription/translation within these cells (Belleannée et al 2013, Belleannée 2015. Of interest here is that miR-145 is one of several known microRNAs that target and regulate expression of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel (Gillen et al 2011), an anion-selective channel expressed in the epididymis and sperm (Diao et al 2013).…”

“…Epididymosomal microRNAs from let-7 and miR-200 families as well as miR-26a, miR-103 and miR-191 were present in high abundance in both epididymosomal populations (Belleannée et al 2013). Additionally, miR-145, miR-143, miR-214 and miR-199 were present in higher amounts in epididymosomes from caput, while miR-654, miR-1224 and miR-395 are higher in epididymosomes collected from the cauda region (Belleannée et al 2013). Moreover, epididymosomes secreted within the epididymis intraluminal environment can be taken up by surrounding epithelial cells possibly regulating transcription/translation within these cells (Belleannée et al 2013, Belleannée 2015.…”

“…In addition to proteins, epididymosomes carry microRNAs within epididymal fluid. Belleannée et al (2013) demonstrated that bovine epididymosomes collected from the epididymal caput (head) and cauda (tail) regions contain different microRNA profiles and do not always reflect the repertoire present in epididymal cells. Epididymosomal microRNAs from let-7 and miR-200 families as well as miR-26a, miR-103 and miR-191 were present in high abundance in both epididymosomal populations (Belleannée et al 2013).…”