Maternal Sleep Loss During Fetal Development Alters Offspring Endocrine Responses to Stress Throughout Life

The hypothalamic-pituitary-adrenal (HPA) axis releases glucocorticoids, including corticosterone (CORT), in response to stress. CORT then negatively feeds back to inhibit its own production by binding to glucocorticoid receptors (GRs) in the hypothalamus and pituitary gland. The HPA axis is subject to “programming” by abnormal stimuli during early development, which may permanently alter how the HPA axis responds to stress. These altered responses have been linked to an increased risk for human psychiatric and metabolic disorders in later life, but the mechanism by which this happens is not fully understood. This study tests the hypothesis that changes to GR expression patterns persisting into adulthood may be playing a role using mice as a model. Pregnant mice were exposed to one of two treatments: 24h of sleep deprivation (SD) or no sleep deprivation. This produced maternally sleep deprived (MSD) pups and non-maternally sleep deprived pups (No-MSD), which were reared to adulthood (\u3e8 weeks of age). Offspring from each group were then exposed to either 24h SD (OSD) or no SD (no-OSD). Hypothalami, hippocampi, liver, and adrenal tissue were taken from these resulting four groups of mice (1. No-MSD:OSD, 2. No-MSD:No-OSD, 3. MSD:OSD, 4. MSD:No-OSD) and RT-PCR was conducted to examine relative GR expression. Mice in the MSD:OSD group showed significant GR reduction in the hypothalamus compared to other groups. Both No-MSD:OSD and MSD:OSD groups showed significant GR reduction in the hippocampus. No significant changes were found in the liver. No-MSD:OSD, MSD:OSD, and MSD:No-OSD groups all showed significant GR reduction in the adrenal glands compared to No-MSD:No-OSD animals. These data provide evidence that acute stress during pregnancy can alter the offspring’s baseline HPA axis function and HPA axis functioning in response to stress. These alterations to how an organism restores homeostasis by activation of the HPA axis when facing a stressor could contribute to the development of disease