Intergenerational effects of paternal predator cue exposure on behavior, stress reactivity, and neural gene expression

Predation threat impacts prey behavior, physiology, and fitness. Stress-mediated alterations to the paternal epigenome can be transmitted to offspring via the germline, conferring a potential advantage to offspring in predator-rich environments. While intergenerational epigenetic transmission of paternal experience has been demonstrated in mammals, how paternal predator exposure might alter offspring phenotypes across development is unstudied. We exposed male mice to a predator odor (2,4,5-trimethylthiazoline, TMT) or a neutral odor (banana extract) prior to mating and measured offspring behavioral phenotypes throughout development, together with adult stress reactivity and candidate gene expression in the prefrontal cortex, hippocampus, amygdala, and hypothalamus. We predicted that offspring of TMT-exposed males would be less active, would display elevated anxiety-like behaviors, and would have a more efficient stress response relative to controls, phenotypes that should enhance predator avoidance in a high predation risk environment. Unexpectedly, we found that offspring of TMT-exposed males are more active, exhibit less anxiety-like behavior, and have decreased baseline plasma corticosterone relative to controls. Effects of paternal treatment on neural gene expression were limited to the prefrontal cortex, with increased mineralocorticoid receptor expression and a trend towards increased Bdnf expression in offspring of TMT-exposed males. These results suggest that fathers exposed to predation threat produce offspring that are buffered against non-acute stressors and, potentially, better adapted to a predator-dense environment because they avoid trade-offs between predator avoidance and foraging and reproduction. This study provides evidence that ecologically relevant paternal experience can be transmitted through the germline, and can impact offspring phenotypes throughout development. •Anxiety-like behavior is reduced in experimental offspring of predator-stressed males.•Baseline corticosterone is reduced in experimental offspring.•Mineralocorticoid receptor expression is higher in experimental offspring brains.•Developmental shifts in anxiety-like behavior differ by sex in experimental offspring.•Paternal predation risk exposure buffers offspring response to non-acute stress.