Maternal ozone exposure and differential cardiometabolic outcomes in aging male and female offspring.

Fetal development is a vulnerable life stage for exposure to environmental stressors. Gestational exposure to ozone (O3) has been shown to compromise fetal growth, predisposing offspring to increased risk of pulmonary and metabolic dysfunction later in life. However, the cardiovascular consequences of maternal O3 exposure on offspring health remain uncharacterized. Herein, pregnant Long-Evans rats were exposed to 0.8 ppm O3 for 4 h each day on gestation day (GD) 5 and 6. Following weaning, male and female offspring were monitored for cardiometabolic health for up to ∼5 months of age. Although there were little-to-no changes in most metabolic endpoints (e.g., growth, food intake, body composition, or glucose tolerance), offspring from O3 exposed dams had an altered respiratory exchange ratio at ∼4 months old that differed by sex. Furthermore, female offspring had adipocyte hyperplasia in the retroperitoneal depot, effects that were not evident in male offspring. Males from O3-exposed dams had altered cardiac structure and function, including left ventricular wall thickening and increased ejection fraction and fractional shortening. Females from O3-exposed dams, on the other hand, had decreased myocardial performance attributed to shortened aortic ejection. RNAseq on hearts from GD 21 fetuses revealed sexually dimorphic effects of maternal O3 exposure on cardiac gene expression, consistent with altered structure and function that was present in adulthood. Collectively, these findings demonstrate that peri-implantation O3 exposure increases the risk of multiple adverse effects, including cardiac dysfunction, in adulthood.