Chronic glucocorticoid exposure in early development leads to neuroendocrine, metabolic, and immune dysregulation in adult zebrafish

Chronic early life stress can affect development of the neuroendocrine stress system, leading to its persistent dysregulation and consequently increased disease risk in adulthood. One contributing factor is thought to be epigenetic programming in response to chronic glucocorticoid exposure during early development. We have previously shown that zebrafish embryos treated chronically with cortisol develop into adults with constitutively elevated whole body cortisol and aberrant immune gene expression. The objective of the experiments reported here was to further characterize the phenotype of those adults. We find that adult zebrafish derived from cortisol-treated embryos have aberrant cortisol tissue distribution and dynamics, which correlate with differential transcriptional activity of key glucocorticoid-responsive regulatory genes klf9 and fkbp5 in blood and brain. Overall design: Genome-wide chromatin accessiblity was assayed from blood samples taken from 6 individual adult zebrafish. For these fish, DMSO (n = 3) or 1 micromolar cortisol (n = 3) was added to larval medium for first 5 days of development and then maintained to adulthood under normal conditions.