학술논문
Involvement of circulating factors in the transmission of paternal experiences through the germline.
Document Type
Academic Journal
Author
van Steenwyk G; Laboratory of Neuroepigenetics, Brain Research Institute, Medical Faculty of the University of Zurich, Zurich, Switzerland.; Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.; Zurich Neuroscience Center, ETH Zurich and University of Zurich, Zurich, Switzerland.; Gapp K; Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.; Zurich Neuroscience Center, ETH Zurich and University of Zurich, Zurich, Switzerland.; Laboratory of Molecular and Behavioral Neuroscience, ETH Zurich, Zurich, Switzerland.; Gurdon Institute, University of Cambridge, Cambridge, UK.; Wellcome Trust Sanger Institute, Hinxton, UK.; Department of Genetics, University of Cambridge, Cambridge, UK.; Jawaid A; Laboratory of Neuroepigenetics, Brain Research Institute, Medical Faculty of the University of Zurich, Zurich, Switzerland.; Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.; Zurich Neuroscience Center, ETH Zurich and University of Zurich, Zurich, Switzerland.; Laboratory of Translational Research in Neuropsychiatric Disorders, BRAINCITY Nencki-EMBL Center of Excellence for Neural Plasticity and Brain Disorders, Warsaw, Poland.; Germain PL; Laboratory of Neuroepigenetics, Brain Research Institute, Medical Faculty of the University of Zurich, Zurich, Switzerland.; Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.; Statistical Bioinformatics Group, Swiss Institute of Bioinformatics, Zürich, Switzerland.; Manuella F; Laboratory of Neuroepigenetics, Brain Research Institute, Medical Faculty of the University of Zurich, Zurich, Switzerland.; Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.; Zurich Neuroscience Center, ETH Zurich and University of Zurich, Zurich, Switzerland.; Tanwar DK; Laboratory of Neuroepigenetics, Brain Research Institute, Medical Faculty of the University of Zurich, Zurich, Switzerland.; Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.; Zurich Neuroscience Center, ETH Zurich and University of Zurich, Zurich, Switzerland.; Statistical Bioinformatics Group, Swiss Institute of Bioinformatics, Zürich, Switzerland.; Zamboni N; Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.; Gaur N; Laboratory of Neuroepigenetics, Brain Research Institute, Medical Faculty of the University of Zurich, Zurich, Switzerland.; Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.; Zurich Neuroscience Center, ETH Zurich and University of Zurich, Zurich, Switzerland.; Efimova A; Laboratory of Neuroepigenetics, Brain Research Institute, Medical Faculty of the University of Zurich, Zurich, Switzerland.; Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.; Zurich Neuroscience Center, ETH Zurich and University of Zurich, Zurich, Switzerland.; Thumfart KM; Laboratory of Neuroepigenetics, Brain Research Institute, Medical Faculty of the University of Zurich, Zurich, Switzerland.; Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.; Zurich Neuroscience Center, ETH Zurich and University of Zurich, Zurich, Switzerland.; Miska EA; Gurdon Institute, University of Cambridge, Cambridge, UK.; Wellcome Trust Sanger Institute, Hinxton, UK.; Department of Genetics, University of Cambridge, Cambridge, UK.; Mansuy IM; Laboratory of Neuroepigenetics, Brain Research Institute, Medical Faculty of the University of Zurich, Zurich, Switzerland.; Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.; Zurich Neuroscience Center, ETH Zurich and University of Zurich, Zurich, Switzerland.
Source
Publisher: Nature Publishing Group Country of Publication: England NLM ID: 8208664 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1460-2075 (Electronic) Linking ISSN: 02614189 NLM ISO Abbreviation: EMBO J Subsets: MEDLINE
Subject
Language
English
Abstract
Environmental factors can change phenotypes in exposed individuals and offspring and involve the germline, likely via biological signals in the periphery that communicate with germ cells. Here, using a mouse model of paternal exposure to traumatic stress, we identify circulating factors involving peroxisome proliferator-activated receptor (PPAR) pathways in the effects of exposure to the germline. We show that exposure alters metabolic functions and pathways, particularly lipid-derived metabolites, in exposed fathers and their offspring. We collected data in a human cohort exposed to childhood trauma and observed similar metabolic alterations in circulation, suggesting conserved effects. Chronic injection of serum from trauma-exposed males into controls recapitulates metabolic phenotypes in the offspring. We identify lipid-activated nuclear receptors PPARs as potential mediators of the effects from father to offspring. Pharmacological PPAR activation in vivo reproduces metabolic dysfunctions in the offspring and grand-offspring of injected males and affects the sperm transcriptome in fathers and sons. In germ-like cells in vitro, both serum and PPAR agonist induce PPAR activation. Together, these results highlight the role of circulating factors as potential communication vectors between the periphery and the germline.
(© 2020 The Authors. Published under the terms of the CC BY 4.0 license.)
(© 2020 The Authors. Published under the terms of the CC BY 4.0 license.)