Uterine Artery Flow and Offspring Growth in Long-Evans Rats following Maternal Exposure to Ozone during Implantation

Colette N Miller, Janice A Dye, Allen D Ledbetter, Mette C Schladweiler, Judy H Richards, Samantha J Snow, Charles E Wood, Andres R Henriquez, Leslie C Thompson, Aimen K Farraj, Mehdi S Hazari, Urmila P Kodavanti
Environmental Health Perspectives2017
BACKGROUND: Epidemiological studies suggest that increased ozone exposure during gestation may compromise fetal growth. In particular, the im- plantation stage of pregnancy is considered a key window of susceptibility for this outcome. OBJECTIVES: The main goals of this study were to investigate the effects of short-term ozone inhalation during implantation on fetal growth outcomes and to explore the potential for alterations in uterine arterial flow as a contributing mechanism. METHODS: Pregnant Long-Evans rats were exposed to filtered air, 0:4ppm ozone, or 0:8ppm ozone for 4 h/d during implantation, on gestation days (GD) 5 and 6. Tail cuff blood pressure and uterine artery Doppler ultrasound were measured on GD 15, 19, and 21. To assess whether peri- implantation ozone exposure resulted in sustained pulmonary or systemic health effects, bronchoalveolar lavage fluid, serum metabolic and inflamma- tory end points, and kidney histopathology were evaluated in dams at GD 21. Growth parameters assessed in GD 21 offspring included fetal weight, length, and body composition. RESULTS: Measures of maternal uterine arterial flow, including resistance index and mean velocity, indicated that resistance increased between GD 15 and GD 21 in 0:8ppm dams but decreased in controls, although absolute values were similar in both groups on GD 21. Ozone-exposed dams also had lower serum glucose and higher free fatty acid concentrations than controls on GD 21. On GD 21, both male and female offspring had lower body weight than controls, and pooled subsets of 3 male and 3 female fetuses from litters exposed to 0:8ppm ozone had lower lean mass and fat mass than pooled control offspring. CONCLUSIONS: Findings from our experimental model suggest that the offspring of dams exposed to ozone during implantation had reduced growth compared with controls, possibly as a consequence of ozone-induced vascular dysfunction.
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