Advancing paternal age is associated with deficits in social and exploratory behaviors in the offspring: a mouse model

Abstract

Background: Accumulating evidence from epidemiological research has demonstrated an association between advanced paternal age and risk for several psychiatric disorders including autism, schizophrenia and early-onset bipolar disorder. In order to establish causality, this study used an animal model to investigate the effects of advanced paternal age on behavioural deficits in the offspring.

Methods: C57BL/6J offspring (n = 12 per group) were bred from fathers of two different ages, 2 months (young) and 10 months (old), and mothers aged 2 months (n = 6 breeding pairs per group). Social and exploratory behaviors were examined in the offspring.

Principal findings: The offspring of older fathers were found to engage in significantly less social (p = 0.02) and exploratory (p = 0.02) behaviors than the offspring of younger fathers. There were no significant differences in measures of motor activity.

Conclusions: Given the well-controlled nature of this study, this provides the strongest evidence for deleterious effects of advancing paternal age on social and exploratory behavior. De-novo chromosomal changes and/or inherited epigenetic changes are the most plausible explanatory factors.

Figure 1. Results of social behavioral data from male offspring of young fathers (n = 12) and old fathers (n = 12).

* shows a p-value of less than 0.05, † shows p-value of 0.06. A. Mean time (±SEM) displaying all social behaviors toward a conspecific mouse (broken down into components in B, C and D). B. Mean time (±SEM) displaying allogrooming behavior towards a conspecific mouse. C. Mean time (±SEM) displaying anogenital sniffing behavior towards a conspecific mouse. D. Mean time (±SEM) displaying sniffing behavior towards a conspecific mouse.

Figure 2. Results of holeboard and open field data from male offspring of young fathers (n = 12) and old fathers (n = 12).

* shows a p-value of less than 0.05. A. Mean number of nose pokes (±SEM) into holes in the holeboard trial. B. Mean time spent in each area of arena (±SEM) in the open field task.