Fetal growth outcomes following peri-implantation exposure of Long-Evans rats to noise and ozone differ by sex

Abstract

BackgroundExposure to air pollution and high levels of noise have both been independently associated with the development of adverse pregnancy outcomes including low birth weight. However, exposure to such environmental stressors rarely occurs in isolation and is often co-localized, especially in large urban areas.MethodsThe purpose of this study was to compare the effects of combined exposure to noise (N) or ozone (O3), compared to either exposure alone. Long-Evans dams were exposed to air or 0.4 ppm ozone for 4 h on gestation day (GD) 5 and 6, coinciding with implantation receptivity. A subset of dams from each exposure group was further exposed to intermittent white noise (~ 85 dB) throughout the dark cycle following each inhalation exposure (n = 14 − 16/group). Uterine artery ultrasound was performed on GD 15 and 21. Fetal growth characteristics and indicators of placental nutrient status were measured at GD 21.ResultsExposure to ozone + quiet (O3 + Q) conditions reduced uterine arterial resistance at GD 15 compared to air + quiet (A + Q) exposure, with no further reduction by GD 21. By contrast, exposure to air + noise (A + N) significantly increased uterine arterial resistance at both GD 15 and 21. Notably, while peri-implantation exposure to O3 + Q conditions reduced male fetal weight at GD 21, this effect was not observed in the air + noise (A + N) or the ozone + noise (O3 + N) exposure groups. Fetal weight in female offspring was not reduced by ozone exposure alone (O3 + Q), nor was it affected by air + noise (A + N) or by combined ozone + noise (O3 + N) exposure.ConclusionsThese data indicate that exposure to ozone and noise differentially impact uterine blood flow, particularly at mid-gestation, with only ozone exposure being associated with sex-dependent fetal growth retardation in male offspring.

Ozone-induced fetal growth restriction in rats is associated with sexually dimorphic placental and fetal metabolic adaptation

“…As in our previous reports [ 16 , 30 , 31 ], 0.8 ppm ozone inhalation for 4 h on the mornings of GDs 5 and 6 induced acute reductions in maternal food intake and body weight gain ( Table S2 ). However, peri-implantation ozone exposure had no effect on total gestational food intake, extrauterine body weight gain, or major litter characteristics such as the litter size and sex distribution ( Table S2 ).…”

“…Prenatal exposure to air pollution is an emerging risk factor for the development of IUGR [ 4 ]. In our studies, we have consistently reported an enhanced male severity to growth restriction induced by peri-implantation inhalation to the gaseous air pollutant ozone [ 16 , 30 , 31 ]. Because of the exposure timing and chemistry of ozone, suppressed fetal growth is unlikely to be due to direct embryonic exposure to ozonation products (for example, lipid peroxides).…”

“…Thus, we hypothesize that the concentrations of varying transporters in the placenta not only differ by sex but are also likely to adapt to subsequent stressors differentially according to the sex of the fetus. While our model is not one of maternal undernutrition, based on our previous work demonstrating impaired uterine blood flow in mid-to-late gestation [ 16 , 30 , 31 ], we suspect that nutrient availability to the placenta may be blunted. We propose that the placentae from males may adapt to increase nutrient transport in the face of fetal growth restriction and/or impaired blood supply, rendering them more susceptible to lipotoxicity unless compensatory efforts to expend excess lipids are not upregulated (for example, fatty acid oxidation).…”

“…Implantation has been identified as a sensitive window to adverse pregnancy outcomes, as suboptimal trophoblast invasion can impair placentation and uterine and spiral arterial remodeling [ 28 ]. Accordingly, acute ozone exposure during implantation receptivity appears to induce fetal growth restriction in part through trophoblast dysfunction [ 29 ] and by impeding uterine arterial blood flow during the second half of gestation [ 16 , 30 , 31 ]. Generally, unhealthy ozone levels have been noted in tropical industrialized areas.…”

Prenatal ozone exposure programs a sexually dimorphic susceptibility to high‐fat diet in adolescent Long Evans rats

“…To investigate the impacts of ozone-induced FGR on the metabolic sensitivity in offspring, the 0.8 ppm concentration was selected for this study as lower concentrations (0.4 ppm) produce weight deficits only in male fetuses. 21,23 A reported four-to fivefold difference in heavy ( 18 O-labeled) reaction products in the lung exists between resting rats and intermittently exercising humans following ozone exposure. 35 Hence, the 0.8 ppm ozone concentration used herein corresponds to an approximated 0.16 ppm exposure in exercising humans, which is double the 2015 US EPA 0.07 ppm ozone standard.…”