Acute heat stress response in male and female mouse offspring perinatally exposed to cadmium or high fructose diet

Early-life stressors may increase susceptibility to adverse environments in adulthood. The aim of this study was to assess homeostatic responses to a physical stressor, heat, in offspring perinatally exposed to environmental and/or dietary stressors. Female CD-1-mice were exposed to 0 ppm cadmium (Cd) with control diet, Cd (0.5 ppm in drinking water with control diet), or 0 ppm Cd with 59% high-fructose (HFr) diet three-weeks pre-mating through postnatal day 16. Offspring (17-21-week-old) were exposed 3 hr to either room-temperature, RT, 21°C; mid-temperature, MT, 30°C; or high-temperature, HT, 37°C (<i>n</i> = 12/sex/group). Maternal HFr reduced postnatal bodyweight in both sexes. Cadmium-exposed males exhibited lower HDL and cholesterol levels, whereas females displayed increased adrenocorticotrophic hormone (ACTH) and leptin levels. HT elevated serum triglycerides concentrations, reduced lymphocyte number, and increased neutrophils regardless of developmental exposure in both sexes. HT elevated serum free fatty acids levels in offspring with exacerbation in Cd and HFr females. HT reduced levels of ACTH and glucose and increased growth hormone in HFr males but decreased glucose in Cd-exposed females. HT-induced immune cell changes were attenuated in HFr males. In females, leptin levels were elevated in HT controls and lowered in HT+HFr with decreased glucose observed in HT+Cd. HT diminished prolactin concentrations in controls and HT+HFr but not Cd-exposed females. HT induced an acute neuroendocrine stress response and associated metabolic/immune changes which were selectively modified by sex and developmental exposure to Cd or HFr diet.