1. Behavioural traits propagate across generations via segregated iterative-somatic and gametic epigenetic mechanisms.
- Author
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Mitchell E, Klein SL, Argyropoulos KV, Sharma A, Chan RB, Toth JG, Barboza L, Bavley C, Bortolozzi A, Chen Q, Liu B, Ingenito J, Mark W, Dudakov J, Gross S, Di Paolo G, Artigas F, van den Brink M, and Toth M
- Subjects
- 8-Hydroxy-2-(di-n-propylamino)tetralin pharmacology, Animals, Anxiety genetics, Anxiety psychology, DNA Methylation genetics, Disease Models, Animal, Female, Gametogenesis physiology, Genomic Imprinting physiology, Hypothermia chemically induced, Hypothermia genetics, Hypothermia psychology, Male, Metabolomics methods, Mice, Mice, Knockout, Models, Animal, Penetrance, Phenotype, Receptor, Serotonin, 5-HT1A genetics, Receptor, Serotonin, 5-HT1A metabolism, Serotonin Receptor Agonists pharmacology, Stress, Psychological genetics, Stress, Psychological psychology, Behavior, Animal physiology, Epigenesis, Genetic, Germ Cells physiology, Maternal Inheritance physiology
- Abstract
Parental behavioural traits can be transmitted by non-genetic mechanisms to the offspring. Although trait transmission via sperm has been extensively researched, epidemiological studies indicate the exclusive/prominent maternal transmission of many non-genetic traits. Since maternal conditions impact the offspring during gametogenesis and through fetal/early-postnatal life, the resultant phenotype is likely the aggregate of consecutive germline and somatic effects; a concept that has not been previously studied. Here, we dissected a complex maternally transmitted phenotype, reminiscent of comorbid generalized anxiety/depression, to elementary behaviours/domains and their transmission mechanisms in mice. We show that four anxiety/stress-reactive traits are transmitted via independent iterative-somatic and gametic epigenetic mechanisms across multiple generations. Somatic/gametic transmission alters DNA methylation at enhancers within synaptic genes whose functions can be linked to the behavioural traits. Traits have generation-dependent penetrance and sex specificity resulting in pleiotropy. A transmission-pathway-based concept can refine current inheritance models of psychiatric diseases and facilitate the development of better animal models and new therapeutic approaches.
- Published
- 2016
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