Timing-dependent effects of elevated maternal glucocorticoids on offspring brain gene expression in a wild small mammal

Abstract An increase in maternal stress during offspring development can have cascading, life-long impacts on offspring behavior and physiology, which can vary depending on the timing of exposure to the stressor. By responding to stressors through increasing production of glucocorticoids (GCs), the hypothalamic-pituitary-adrenal (HPA) axis is a key mediator of maternal effects – both on the side of the mother and the offspring. At a molecular level, maternal effects are thought to be mediated through modifying transcription of genes, particularly in the brain. To better understand the evolutionary implications of maternal effects, more studies are needed on mechanisms of maternal effects in wild populations. To test how the timing of maternal stress impacts gene expression in the brains of offspring, we treated free-ranging North American red squirrels ( Tamiasciurus hudsonicus ) with GCs during late pregnancy or early lactation and collected brains from offspring around weaning. We used RNA-sequencing to measure gene expression in the hypothalamus and hippocampus. We found small differences in gene expression between GC-treated and control individuals suggesting long-term effects of the GC treatment on neural gene transcription. The general patterns of gene regulation across the transcriptome were consistent between the pregnancy and lactation-treated individuals. However, the number of significantly differentially expressed genes was higher in the lactation treatment group. These results support the idea that maternal stress affects neural gene expression in offspring, and these effects are dependent on timing. Our findings add valuable insight into the impact of maternal hormones on neural transcriptomics in a wild population.