Small RNAs are trafficked from the epididymis to developing mammalian sperm

SUMMARY

The biogenesis of the RNA payload of mature sperm is of great interest, as RNAs delivered to the zygote at fertilization can affect early development. Here, we tested the hypothesis that small RNAs are trafficked to mammalian sperm during the process of post-testicular maturation in the epididymis. By characterizing small RNA dynamics during germ cell maturation in mice, we confirm and extend prior observations that sperm undergo a dramatic switch in RNA payload from piRNAs to tRNA fragments (tRFs) upon exiting the testis and entering the epididymis. Small RNA delivery to sperm could be recapitulated in vitro by incubating testicular spermatozoa with caput epididymosomes. Finally, tissue-specific metabolic labeling of RNAs in intact mice definitively shows that mature sperm carry RNAs that were originally synthesized in the epididymal epithelium. These data demonstrate that soma-germline RNA transfer occurs in male mammals, most likely via vesicular transport from the epididymis to maturing sperm.

In-Brief/eTOC Blurb

Recent studies suggest that sperm carry RNAs first synthesized in epididymal somatic cells. Sharma et al. test this hypothesis, characterizing small RNA population dynamics during sperm maturation. They show that caput epididymosomes can deliver RNAs to immature sperm in vitro and track RNAs in vivo from epididymis to sperm using metabolic labeling.