Citation:

Miller, C., E. Stewart, Kathy Mcdaniel, P. Phillips, M. Schladweiler, J. Richards, M. Valdez, C. Gordon, U. Kodavanti, AND J. Dye. Acute exposures, lifelong consequences: ozone inhalation during implantation receptivity alters energy balance in offspring. US DOHaD, Chapel Hill, NC, October 01 - 02, 2018.

Impact/Purpose:

We previously reported that exposure to ozone during implantation receptivity impairs uterine arterial blood flow with subsequent growth restriction of the fetus. Growth restricted infants are at a greater risk of cardiometabolic disease as they age. Accordingly, we hypothesized that offspring from ozone-exposed dams would be at an increased risk of metabolic disease.

Description:

Background: We previously reported that exposure to ozone during implantation receptivity impairs uterine arterial blood flow with subsequent growth restriction of the fetus. Growth restricted infants are at a greater risk of cardiometabolic disease as they age. Accordingly, we hypothesized that offspring from ozone-exposed dams would be at an increased risk of metabolic disease. Methods: Pregnant, Long-Evans rats were exposed to filtered air or 0.8 ppm ozone, 4 hours/day on gestation days 5 and 6 (n=5-6 dams/group). At postnatal day 45, male and female offspring were challenged with a 10% low-fat diet (LFD) or 45% high-fat diet (HFD) for 72-hours (n=10-12/exposure/diet/sex). Caloric intake and body weight were assessed daily, and changes in body composition were measured by magnetic resonance. Basal metabolic rate was determined for the final 22 hours of the study. Hypothalamic genes related to food intake, inflammation, and stress were assessed by qPCR. Data were analyzed by two-way ANOVA followed by Tukey’s HSD within each sex. Results: Offspring from ozone-exposed dams had increased caloric intake when fed a HFD compared to similarly-fed offspring from air-exposed dams. While the increased energy consumption did not alter body weight in females, males of the ozone-exposed, HFD-group had increased weight and fat deposition over the 72-hour period compared to controls. Ozone exposure in dams was associated with reduced metabolic rate in offspring, suggestive of decreased whole-body energy expenditure, and elevations in circulating leptin and insulin. Lastly, males from ozone-exposed dams had disrupted expression of the appetite-regulating genes, Cartpt and Npy, and genes related to the neuroendocrine stress axis, Adrb2 and Nr3c1; whereas females showed little differences. Conclusion: These data suggest that acute ozone exposure early in gestation is associated with disrupted energy balance in adolescent offspring, which may increase their susceptibility to obesity when in an adverse nutritional environment.

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