Effects of maternal endotoxin treatment on offspring hypothalamic-pituitary-adrenal axis and fever response.

摘要

Adverse uterine environments during pregnancy have been shown to alter fetal programming of the HPA axis leaving the offspring more susceptible to disease in adulthood. Therefore, the purpose of this thesis was to investigate the effects of maternal endotoxin exposure on offspring HPA axis and fever responses. On day 135 of gestation ewes were challenged with 1.2 microg/kg endotoxin, 400 ng/kg endotoxin for 3 consecutive days, or saline to mimic bacterial infection. The offspring's HPA axis and fever responses to an endotoxin challenge as well as during neuropeptide and additional stressor challenges were measured during adulthood. The maternal high dose endotoxin treatment increased the cortisol and eye temperature response in their offspring compared to the other treatment groups. The ACTH challenge suggested that re-programming of these offspring may be occurring at the level of the adrenal gland, as there was no difference observed following an AVP+CRF challenge. Overall, this thesis provided insight into various aspects of fetal programming providing new areas for further investigation.