Testosterone and Glucocorticoid-Mediated Developmental Programming of Stress Systems in Mice

Elevated prenatal testosterone affects social and anxiety-like behaviour in a similar manner to early-life stress in mice. We hypothesize that prenatal testosterone may alter stress sensitivity in a similar manner to prenatal glucocorticoids. We treated mice with a low dose of testosterone, dexamethasone (a synthetic glucocorticoid) or sesame oil vehicle during mid to late pregnancy. We assessed the expression of stress sensitive genes and microRNAs on the day of birth and at one week of age and hippocampal dendritic morphology in adulthood. We found that heightened prenatal testosterone decreased miRNA-124 expression on the day of birth. Prenatal dexamethasone increased both mineralocorticoid and glucocorticoid receptor mRNA at one week. In adulthood, hippocampal branching was affected by each treatment in a region and sex dependent manner. Our study may have implications for understanding potential neurobiological mechanisms of stress-related disorders resulting from heightened testosterone of glucocorticoids during early development.