Citation:

Rentschler, K., K. Das, C. Lau, C. Miller, M. Schladweiler, R. Grindstaff, L. Strader, G. Palmer, W. Williams, P. Evansky, AND U. Kodavanti. Prenatal Cadmium or High Fructose Exposure Alters the Physiological Stress Response to High Temperature in a Sex-Dependent Manner. Society of Toxicology, Salt Lake City, UT, March 10 - 14, 2024.

Impact/Purpose:

Populations living near Superfund sites are exposed to heavy metals as a byproduct of anthropogenic waste. Individuals dwelling near Superfund sites may lack accessibility to healthy dietary choices and may consume diets high in fructose. The combination of environmental pollutant exposure and excessive high fructose consumption can lead to adverse developmental changes and chronic disease later in life, which may be exacerbated by external stressors. Thus, we contrasted prenatal cadmium exposure or high fructose diet in CD-1 mice in the context of temperature stress. Little is known on how prenatal stressors may impact the physiological response to heat stress while including sex as a biological variable.Thus, we contrasted prenatal cadmium exposure or high fructose diet in CD-1 mice in the context of temperature stress. Little is known on how prenatal stressors may impact the physiological response to heat stress while including sex as a biological variable. The effects of prenatal exposure to environmental or dietary stressors and later life high temperature, may alter the thermoregulatory stress response, and may be an indicator for metabolic dysfunction.  

Description:

Background and Purpose: Populations living near Superfund sites are exposed to heavy metals as a byproduct of anthropogenic waste. Individuals dwelling near Superfund sites may lack accessibility to healthy dietary choices and may consume diets high in fructose. The combination of environmental pollutant exposure and excessive high fructose consumption can lead to adverse developmental changes and chronic disease later in life, which may be exacerbated by external stressors. Thus, we contrasted prenatal cadmium exposure or high fructose diet in CD-1 mice in the context of temperature stress. Little is known on how prenatal stressors may impact the physiological response to heat stress while including sex as a biological variable. We hypothesized that prenatal exposure to cadmium or high fructose diet alters the normal response to heat stress when compared to controls with possible sex differences in hormone and serum biomarkers. Methods: CD-1 mice were bred, and pregnant dams were given either 1) water and control diet (AIN-93G), 2) cadmium in drinking water (0.5 ppm) and control diet, or 3) water and high fructose (60%; D20120701) diet two weeks prior to mating through offspring postnatal day 10 (PND10). From PND10 through completion of experiment, all animals were given regular water and a control diet. Between 17-21 weeks of age, animals underwent an acute exposure (3 hours) to one of three temperatures (room temperature, RT, 22 oC; mid temperature, Tn, 31 oC; or high temperature, HT, 37 oC) in climate-controlled Hazelton-type inhalation chambers for 3 hrs. Blood samples were then collected within 2 hours after exposure (n=12/sex/group). Clinical chemistry biomarkers and pituitary hormones were analyzed in serum/plasma samples. Data were analyzed by a generalized linear model with Sidak’s post hoc test and where appropriate, were log transformed. Conclusion: Clinical chemistry changes in serum occurred during HT exposure, which was an expected adaptive stress response. Prenatal cadmium exposure in males blunted the adaptive response of reduced blood lymphocyte percentage caused by high temperature exposure when compared to controls, a phenomenon which was also observed in females prenatally exposed to fructose. Only males prenatally exposed to cadmium had an increased number of serum neutrophils, suggesting an enhanced immunological activation when exposed to HT. Basal sex differences were observed in free fatty acid elevation with HT, whereas triglyceride levels were elevated for all groups in both sexes. Prenatal high fructose diet increased serum growth hormone changes across all temperature conditions, indicating a greater risk of abnormal growth patterns and metabolic dysfunction. A failure in the reduction in prolactin levels seen with high temperature exposure in females prenatally exposed to cadmium, may indicate an abnormal physiological adaptation to heat stress. Taken together, the effects of prenatal exposure to environmental or dietary stressors and later life high temperature, may alter the thermoregulatory stress response, and may be an indicator for metabolic dysfunction. (This abstract does not necessarily reflect USEPA policy).

Record Details: