Corticosterone exposure causes long-term changes in DNA methylation, physiology, and breeding decisions in a wild bird.

When facing challenges, vertebrates activate an evolutionarily conserved hormonal stress response that can dramatically alter behavior and physiology. Although this response can be costly, conceptual models suggest that it can also recalibrate the stress response system, priming more effective responses to future challenges. Little is known about whether this process occurs in wild animals, particularly in adulthood, and if so, how information about prior experience with stressors is encoded. One potential mechanism is hormonally-mediated changes to DNA methylation. We simulated the spikes in corticosterone that accompany an acute stress response using non-invasive dosing in female tree swallows (Tachycineta bicolor) and monitored the phenotypic effects one year later, and DNA methylation both shortly after treatment and a full year later. The year after treatment, experimental females had stronger negative feedback and initiated breeding earlier - traits that are associated with stress resilience and reproductive performance in our population - and higher baseline corticosterone. We also found that natural variation in stress-induced corticosterone predicted patterns of DNA methylation, including methylation of the MC2R gene, which encodes the adrenocorticotropic hormone receptor. Finally, corticosterone treatment causally influenced methylation on short (1-2 weeks) and long (1 year) time scales; however, many of these changes did not have clear links to functional regulation of the stress response. Taken together, our results are consistent with corticosterone-induced priming of future stress resilience, and support DNA methylation as a potential mechanism. Uncovering the mechanisms linking experience with the response to future challenges has implications for understanding the drivers of stress resilience. SIGNIFICANCEA stress response to an environmental challenge can preserve an individuals fitness and may even prime them to survive similar challenges in the future. What mechanisms underlie priming is unclear, but epigenetic alterations to stress-related genes are one possibility. We experimentally tested whether increasing corticosterone in free-living swallows had lasting phenotypic or epigenetic effects. A year after treatment, females who received corticosterone had altered stress physiology and bred earlier than control birds, traits that are associated with higher fitness. Treatment also altered DNA methylation and methylation of the MC2R gene was correlated with stress physiology. This study adds to a growing body of literature suggesting that epigenetic changes are key to animals response to a changing environment.