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Implication of sperm RNAs in transgenerational inheritance of the effects of early trauma in mice

Nature Neuroscience 17, 667–669 (2014) | Download Citation

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Abstract

Small non-coding RNAs (sncRNAs) are potential vectors at the interface between genes and environment. We found that traumatic stress in early life altered mouse microRNA (miRNA) expression, and behavioral and metabolic responses in the progeny. Injection of sperm RNAs from traumatized males into fertilized wild-type oocytes reproduced the behavioral and metabolic alterations in the resulting offspring.

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Acknowledgements

We thank M. Rassoulzadegan and V. Grandjean for help with the sperm purification, F. Manuella and H. Hörster for assistance with the MSUS paradigm, H. Welzl for help with behavior, G. Vernaz for help with western blotting, R. Tweedie-Cullen and P. Nanni for help with mass spectrometry, A. Patrignani for advice on DNA and RNA quality assessment, and A. Chen and A. Brunner for constructive discussions. This work was supported by the Austrian Academy of Sciences, the University of Zürich, the Swiss Federal Institute of Technology, Roche, the Swiss National Science Foundation, and The National Center of Competence in Research “Neural Plasticity and Repair”. P.S. was supported by a Gonville and Caius College fellowship.

Author information

    • Julien Prados

    Present address: Neuroscience Center, University Geneva, Geneva, Switzerland.

Affiliations

  1. Brain Research Institute, Neuroscience Center Zürich, University of Zürich and Swiss Federal Institute of Technology, Zürich, Switzerland.

    • Katharina Gapp
    • , Ali Jawaid
    • , Johannes Bohacek
    •  & Isabelle M Mansuy

  2. Gurdon Institute, Cambridge, UK.

    • Peter Sarkies
    •  & Eric Miska

  3. Institute of Laboratory Animal Science, University of Zürich, Zürich, Switzerland.

    • Pawel Pelczar

  4. FASTERIS SA, Plan-les-Ouates, Switzerland.

    • Julien Prados
    •  & Laurent Farinelli

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Contributions

K.G. carried out all of the RT-qPCR, behavioral tests, metabolic measurements, and sperm RNA preparation for sequencing libraries and for RNA injection into fertilized oocytes, and part of the sequencing analyses. A.J. performed western blots and cell culture experiments and assisted with metabolic measurements. J.B. carried out the MSUS procedures and produced MSUS mice. J.P. and P.S. performed most RNA sequencing analyses. P.P. carried out the RNA injection experiments. E.M. and L.F. helped design the RNA sequencing analysis. K.G. and I.M.M. designed the study, interpreted the results and wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Isabelle M Mansuy.

Integrated supplementary information

Supplementary figures

  1. 1.

    Size and integrity profile of sperm RNAs used for deep sequencing and injected into fertilized oocytes.

  2. 2.

    SncRNAs in adult sperm.

  3. 3.

    Illustration of short RNA reads in adult mouse sperm.

  4. 4.

    Proportion of 15-30bp reads including or excluding a 16bp specific sequence.

  5. 5.

    Experimental design for MSUS treatment and breeding.

  6. 6.

    Activity on an elevated plus maze.

  7. 7.

    Metabolic profile in F1 MSUS animals.

  8. 8.

    Metabolic profile in F2 MSUS animals.

  9. 9.

    Effect of MSUS on piRNAs in adult sperm.

  10. 10.

    MiRNA expression in hypothalamus and cortex in F1 mice.

  11. 11.

    MiRNAs expression in the hippocampus of F3 animals.

  12. 12.

    Analyses in MSUS-RNAinj males.

  13. 13.

    Performance of the offspring of RNAinj animals on a forced swim.

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1–13 and Supplementary Table 1

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DOI

https://doi.org/10.1038/nn.3695

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