Citation:

Nguyen, H., E. Stewart, Mette C. Schladweiler, H. Ren, A. Fisher, C. Miller, AND J. Dye. Repeated Early Life Ozone Exposure Alters Metabolic Responses in Peri-Adolescent Rats. Society of Toxicology (SOT) Annual Meeting 2022, San Diego, CA, March 27 - 31, 2022.

Impact/Purpose:

Early life exposure to air pollutants may alter fetal development and program susceptibility to environmental stressors later in life. Hence, the purpose of this study was to determine whether peri-implantation ozone (O3) exposure, which results in fetal growth restriction in rodents, exacerbates metabolic effects to repeated O3 inhalation during adolescence. 

Description:

Early life exposure to air pollutants may alter fetal development and program susceptibility to environmental stressors later in life. Hence, the purpose of this study was to determine whether peri-implantation ozone (O3) exposure, which results in fetal growth restriction in rodents, exacerbates metabolic effects to repeated O3 inhalation during adolescence. Pregnant Long-Evans rats were exposed to either filtered air (FA) or 0.8 ppm O3 for 4 hours during implantation receptivity on gestation days 5 – 6. Female and male offspring were weaned on postnatal day 21 and exposed to either FA or 0.4 – 0.8 ppm O3 for 4 hours, once per week, over three consecutive weeks. Following the final post-natal exposure in all offspring, serum was collected for adipokine and metabolic panels, and livers were assessed for alterations in gene expression using RNA-seq (n = 5 – 6/group). Differentially expressed genes (DEGs) were determined by Storey q-value ≤ 0.05. Results revealed no significant differences in serum endpoints for female offspring. However, combined pre- and post-natal O3 exposure resulted in elevated serum glucose (21%) and HOMA-IR (50%) in male offspring compared to FA controls. Serum total cholesterol concentration was also increased in male offspring exposed to O3 either pre-natally only (43%), post-natally only (29%) or both (57%). In female offspring, the combination of the pre- and post-natal O3 exposure resulted in 429 upregulated DEGs and 528 downregulated DEGs. Conversely, pre-natal O3 exposure alone showed the most robust transcriptomic changes in male offspring with 2,161 upregulated DEGs and 1,857 downregulated DEGs compared to FA. In summary, pre-natal O3 exposure resulted in hepatic gene alterations that were apparent in both sexes, with males generally more affected than females. Furthermore, males also showed heightened circulating responses to O3 exposure, with the greatest effects observed in offspring when exposed both pre-natally and post-natally. Together, data suggest that early life exposure to air pollutants may developmentally program metabolic risk related to additional post-natal stressors. Abstract does not reflect U.S. EPA policy.

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