Covariation between glucocorticoid levels and receptor expression modulates embryo development and postnatal phenotypes in gulls.

The hypothalamic-pituitary-adrenocortical axis can translate, through glucocorticoid secretion, the prenatal environment to development to produce phenotypes that match prevailing environmental conditions. However, whether developmental plasticity is modulated by the interaction between circulating glucocorticoids and receptor expression remains unclear. Here, we tested whether covariation between plasma corticosterone (CORT) and glucocorticoid receptor gene (Nr3c1) expression in blood underlies embryonic developmental programming in yellow-legged gulls (Larus michahellis). We examined variations in circulating levels of CORT and the expression and DNA methylation patterns of Nr3c1 in response to two ecologically relevant prenatal factors: adult alarm calls (a cue of predator presence) and changes in prenatal light environment (a cue of competitive disadvantage). We then determined whether embryonic development and postnatal phenotypes were associated with CORT levels and Nr3c1 expression, and explored direct and indirect relationships between the prenatal environment, hormone-receptor covariation, and postnatal phenotypes. Prenatal exposure to alarm calls increased CORT levels and up-regulated Nr3c1 expression in gull chicks, while exposure to light cues reduced both hormone levels and receptor expression. Chicks prenatally exposed to alarm calls showed altered DNA methylation profiles in the Nr3c1 regulatory region, but patterns varied throughout the breeding season and between years. Moreover, our results suggest a negative relationship between DNA methylation and expression in Nr3c1 , at least at specific CpG sites. The interplay between circulating CORT and Nr3c1 expression affected embryo developmental timing and vocalizations, as well as hatchling mass and fitness-relevant behaviours. These findings provide a link between prenatal inputs, glucocorticoid function and phenotypic outcomes, suggesting that hormone-receptor interaction may underlie developmental programming in free-living animals.