Effects of advanced paternal age on trajectories of social behavior in offspring

M. Janecka, A. Manduca, M. Servadio, V. Trezza, R. Smith, J. Mill, L. C. Schalkwyk, A. Reichenberg, C. Fernandes

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Our study is the first investigation of the effects of advanced paternal age (APA) on the developmental trajectory of social behavior in rodent offspring. Given the strong epidemiological association between APA and sexually dimorphic neurodevelopmental disorders that are characterized by abnormalities in social behavior (autism, schizophrenia), we assessed sociability in male and female inbred mice (C57BL/6J) across postnatal development (N=104) in relation to paternal age. We found differences in early social behavior in both male and female offspring of older breeders, with differences in this social domain persisting into adulthood in males only. We showed that these social deficits were not present in the fathers of these offspring, confirming a de novo origin of an altered social trajectory in the offspring generation. Our results, highly novel in rodent research, support the epidemiological observations in humans and provide evidence for a causal link between APA, age-related changes in the paternal sperm DNA and neurodevelopmental disorders in their offspring.

Original languageEnglish
Pages (from-to)443-453
Number of pages11
JournalGenes, Brain and Behavior
Volume14
Issue number6
DOIs
StatePublished - 1 Jul 2015

Keywords

  • De novo mutations
  • Environmental effects
  • Epidemiology
  • Mouse models
  • Neurodevelopment autism
  • Neuroligin
  • Paternal age effects
  • Psychiatry
  • Schizophrenia
  • Social behavior

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