Effects of Development on HPA Function following Pubertal Stress

Abstract

For women, two of the greatest risk factors for affective disorders are adversity experienced during puberty and later becoming pregnant. We have created a translationally relevant mouse model where we address these complex risk factors. Previously, we discovered that pregnant mice (dams) that experienced chronic variable stress (CVS) during puberty display a blunted hypothalamic-pituitary-adrenal (HPA) response when exposed to an acute stressor. Interestingly, this alteration only first becomes apparent during pregnancy, which is a sensitive period for these effects due to normative neuroendocrine changes. Further investigation of the mechanisms underlying this dysfunction revealed altered gene expression in the paraventricular nucleus (PVN) of the hypothalamus, but not in other tissues along the HPA pathway. Until now, we have only examined effects of pubertal stress on HPA function in adult dams. Therefore, effects of pubertal stress on HPA axis function when pregnancy occurs prior to adulthood are unknown. Our study aims to address whether this suppressed HPA activity resulting from pubertal stress is apparent prior to neuroendocrine maturation. Evidenced by increased levels of gonadal hormones and synaptic plasticity in adolescence, endocrine and neural systems responsible for modulating the stress response continue to mature into adulthood. Due to the organizational restructuring of the brain that occurs in both adolescence and pregnancy, I hypothesized that pubertal stress would have differential outcomes for adolescent and adult mothers. Thus, I predicted that there would be an interaction between pubertal stress and age at pregnancy, such that the pubertal stress-induced blunted HPA response would only be observed in adult, pregnant females. My findings show that neither age at pregnancy nor pubertal stress exposure altered HPA activity in pregnant mice. Limitations of this study and suggestions for future studies are discussed.