Early life stress affects the miRNA cargo in epididymal extracellular vesicles in mouse

Sperm RNA can be modified by environmental factors and has been implicated in communicating signals about changes in a fathers environment to the offspring. The RNA composition of sperm is influenced during its final stage of maturation in the epididymis by extracellular vesicles released by epididymal cells. We studied the effect of exposure to stress in postnatal life on the transcriptome of epididymal extracellular vesicles using a mouse model of transgenerational transmission. We found that the small RNA signature of epididymal extracellular vesicles, particularly miRNAs, is altered in adult males exposed to postnatal stress. miRNAs changes correlate with differences in the expression of their target genes in sperm and zygotes generated from that sperm. These results suggest that stressful experiences in early life can have persistent biological effects on the male reproductive tract that may in part be responsible for the transmission of the effects of exposure to the offspring. Summary SentencemiRNA cargo of extracellular vesicles in cauda epididymis is changed by paternal exposure to early life stress, which correlates with differences in the expression of their target genes in sperm and zygotes generated from that sperm