Implication of sperm RNAs in transgenerational inheritance of the effects of early trauma in mice
Mansuy, Isabelle M
Nature Publishing Group
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Gapp, K., Jawaid, A., Sarkies, P., Bohacek, J., Pelczar, P., Prados, J., Farinelli, L., et al. (2014). Implication of sperm RNAs in transgenerational inheritance of the effects of early trauma in mice. Nature, Neuroscience, 17 667-669. https://doi.org/10.1038/nn.3695
Gene-environment interactions are determining factors for the etiology of psychiatric disorders, diabetes and cancer, and are thought to contribute to disease inheritance across generations. Small non-coding RNAs (sncRNAs) are potential vectors at the interface between genes and environment. Here, we report that environmental conditions involving traumatic stress in early life in mice altered microRNAs (miRNAs) expression, and behavioral and metabolic responses in the progeny. Several miRNAs were affected in the serum and brain of both, the traumatized animals and their progeny when adult, but also in the sperm of traumatized males. Injection of sperm RNAs from these males into fertilized wild-type oocytes reproduced the behavioral and metabolic alterations in the resulting offspring. These results strongly suggest that sncRNAs are sensitive to environmental factors in early life, and contribute to the inheritance of traumainduced phenotypes across generations. They may offer potential diagnostic markers for associated pathologies in humans.
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.
Wellcome Trust (092096/Z/10/Z)
External DOI: https://doi.org/10.1038/nn.3695
This record's URL: https://www.repository.cam.ac.uk/handle/1810/247242