Citation:

Miller, C., A. Ledbetter, M. Schladweiler, J. Richards, C. Wood, S. Snow, A. Johnstone, R. Jaskot, A. Henriquez, L. Thompson, A. Farraj, M. Hazari, J. Dye, AND U. Kodavanti. Peri-implantation Ozone Exposure Alters Uterine Artery Flow and Induces Fetal Growth Restriction in Rats. Experimental Biology, Chicago, IL, April 22 - 26, 2017.

Impact/Purpose:

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.

Description:

Epidemiological studies suggest a relationship between air pollutant exposures to various adverse pregnancy outcomes. Elevated ambient ozone levels during the first and second trimesters have demonstrated an increased correlation to 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. Timed-pregnant, Long-Evans female rats were exposed to filtered air, 0.4ppm, or 0.8ppm ozone for 4 hours on the morning of gestational days 5 and 6. Tail cuff blood pressure and Doppler ultrasound of the uterine artery were measured 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 throughout pregnancy, 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. Despite impaired uterine artery flow, inflammatory cytokines in the maternal serum and kidney markers of preeclampsia were not impacted by peri-implantation ozone exposure. At end of gestation both male and female offspring total weight, fat mass, and lean mass were reduced as a result of early gestational ozone exposure. 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 suggests that peri-implantation exposure to ozone adversely impacts uterine artery flow leading to blunted fetal growth without compromising maternal health. While ozone exposure induces the hypothesized etiology of preeclampsia, we have ruled out the stress pathways that lead to maternal hypertension at the end of gestation in our model. We thus propose that an underlying condition, such as obesity in addition to a secondary injury during implantation, such as elevated ambient air pollution, may be necessary to develop preeclampsia. This abstract does not reflect US EPA Policy.

Record Details: