4.5 Article

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

Journal

BIOLOGY OF REPRODUCTION
Volume 105, Issue 3, Pages 593-602

Publisher

OXFORD UNIV PRESS INC
DOI: 10.1093/biolre/ioab156

Keywords

epigenetics; epididymis; epididymosomes; early life stress; extracellular vesicles; miRNAs; sperm

Funding

  1. Swiss National Science Foundation [31003A-135715]
  2. ETH [ETH-10 15-2, ETH-17 13-2]
  3. Slack-Gyr Foundation
  4. Escher Foundation
  5. University Zuric
  6. Swiss Federal Institute of Technology
  7. Swiss Government Excellence Scholarship
  8. ETH Zurich Fellowship [ETH-10 15-2]
  9. Swiss National Science Foundation (SNF) [31003A_135715] Funding Source: Swiss National Science Foundation (SNF)

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Exposure to stress in early postnatal life may alter sperm RNA and have an impact on the small RNA signature of epididymal EVs in adult males. These changes in miRNA could affect gene expression in sperm and zygotes, thereby partly transmitting the effects of stress exposure to offspring.
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 small RNA composition of sperm could be changed during its final stage of maturation in the epididymis by extracellular vesicles (EVs) released by epididymal cells. We studied the effect of exposure to stress in early postnatal life on the transcriptome of epididymal EVs using a mouse model of transgenerational transmission. We found that the small RNA signature of epididymal EVs, particularly miRNAs, is altered in adult males exposed to postnatal stress. In some cases, these miRNA 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. [GRAPHICS] .

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