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 father's 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. small RNA sequencing of cauda epididymosomes from 9-month adult, Control or MSUS males. For MSUS, litters were exposed to unpredictable maternal separation combined with unpredictable maternal stress (MSUS) during the first 14 days after birth (Franklin et al., 2010) and for Control, litters were untouched. Control and MSUS males were sacrificed at postnatal-day 28 and at 9-month old for tissue collection. For cauda epididymosoma sequencing, 5 Control and 5 MSUS samples were used. The sequencing was performed in 2 runs - 1st run without size-selection, 2nd run with miRNA-specific size-selection.