The MicroRNA Signature of Mouse Spermatozoa Is Substantially Modified During Epididymal Maturation

Brett Nixon, Simone J. Stanger, Bettina P. Mihalas, Jackson N. Reilly, Amanda L. Anderson, Sonika Tyagi, Janet E. Holt, Eileen A. McLaughlin

Research output: Contribution to journalArticlepeer-review

154 Citations (Scopus)


In recent years considerable effort has been devoted to understanding the epigenetic control of sperm development, leading to an increased appreciation of the importance of RNA interference pathways, and in particular miRNAs, as key regulators of spermatogenesis and epididymal maturation. It has also been shown that sperm are endowed with an impressive array of miRNA that have been implicated in various aspects of fertilization and embryo development. However, to date there have been no reports on whether the sperm miRNA signature is static or whether it is influenced by their prolonged maturation within the male reproductive tract. To investigate this phenomenon, we employed next-generation sequencing to systematically profile the miRNA signature of maturing mouse spermatozoa. In so doing we have provided the first evidence for the posttesticular modification of the sperm miRNA profile under normal physiological conditions. Such modifications include the apparent loss and acquisition of an impressive cohort of some 113 and 115 miRNAs, respectively, between the proximal and distal epididymal segments. Interestingly, the majority of these changes occur late in maturation and include the uptake of novel miRNA species in addition to a significant increase in many miRNAs natively expressed in immature sperm. Because sperm are not capable of de novo transcription, these findings identify the epididymis as an important site in establishing the sperm epigenome with the potential to influence the peri-conceptual environment of the female reproductive tract, contribute to the inheritance of acquired characteristics, and/or alter the developmental trajectory of the resulting offspring.

Original languageEnglish
Article number91
Pages (from-to)1-20
Number of pages20
JournalBiology of Reproduction
Issue number4
Publication statusPublished - 1 Oct 2015
Externally publishedYes


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