Extracellular Microvesicles miRNAs in Male Reproductive Tract; Possible Functions in Sperm Maturation

Leaving the testis, spermatozoa transit within a long convoluted tubule named epididymis. It is during this journey that the male gamete acquires its fertilizing ability and forward motility properties. The epididymis is anatomically divided in three segments; the proximal caput, the corpus and the bulbous distal cauda. Under androgen control, the epididymis secretes proteins that sequentially modify the male gamete. Extracellular microvesicles named epididymosomes are present in the intraluminal compartment all along the epididymis and have been shown to be involved in the transfer of selected proteins to the maturing spermatozoa. We recently showed that miRNAs are associated with epididymosomes. Using a global microarray approach, we showed that epididymosomes isolated from different epididymal segments possess distinct miRNA signature.  In a given epididymal segment, the population of miRNAs associated with epididymosomes is different form the miRNAs extracted from the corresponding tissue suggesting that miRNAs released in the epididymal epithelium are selectively sorted. Microarray analyses reveal that each epididymal segment is also characterized by a unique transcriptome signature.  In order to evaluate if miRNAs associated with epididymosomes can modulate gene expression along the epididymis, epididymal epithelial cells in primary cell culture were incubated with DilC12-labeled epididymosomes. Flow cytometry analysis revealed that epithelial cells from proximal epididymis incorporate epididymosomes prepared from more distal epididymal segments. Taken together, these results reveal that distinct miRNA repertoires are released in the epididymal intraluminal compartment and could be involved in intercellular communication through the epididymis via extracellular microvesicles named epididymosomes.