Peri‐implantation Ozone Exposure Alters Uterine Artery Flow and Induces Fetal Growth Restriction in Rats

Abstract

Epidemiological studies suggest a relationship between air pollutant exposures and various adverse pregnancy outcomes. Exposure to elevated ambient ozone levels during the first and second trimesters has been associated with increased risk for preeclampsia, gestational diabetes, and intrauterine growth restriction. As many of the adverse pregnancy outcomes are hypothesized to initiate from poor implantation, we sought to determine if an acute exposure to ozone during the implantation period would generate such outcomes later in pregnancy. Timed‐pregnant, Long‐Evans female rats were exposed to filtered air, 0.4ppm, or 0.8ppm ozone for 4 hours on each morning of gestational days 5 and 6. Tail cuff blood pressure and Doppler ultrasound of the uterine artery were measured following the phase of arterial remodeling on gestational days 15, 19, and 21. Rats were euthanized on gestational day 21 and offspring growth parameters were measured. While ozone exposure failed to impact maternal blood pressure at the times measured, multiple indices of blood flow in the uterine artery were adversely impacted as a result of early ozone exposure. Rats exposed to 0.8ppm ozone had increased uterine artery resistance index, systolic to diastolic ratio, pulsatile index, and end diastolic notching as pregnancy advanced compared to air controls. There was no evidence of systemic inflammation or kidney markers of preeclampsia in the dams. Ozone exposure decreased male and female offspring total weight, fat mass, and lean mass at the end of gestation. Further, 7 out of 9 dams exposed to 0.8ppm ozone during implantation had an average female offspring weight under the 10th percentile of air control pregnancies, suggestive of severe intrauterine growth restriction. Together these data suggest that peri‐implantation exposure to ozone adversely impacts uterine artery flow, which may have contributed to blunted fetal growth. These findings suggest a plausible biological mechanism for the epidemiological findings linking air pollutant exposure and adverse pregnancy outcomes. This abstract does not reflect US EPA Policy.Support or Funding InformationThis work was funded by the US EPA.