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Gestational exposure to ozone results in hepatic and systemic metabolic perturbations in male rat offspring
Citation:
Stewart, E., C. Miller, J. Richards, M. Schladweiler, S. Snow, A. Henriquez, U. Kodavanti, AND J. Dye. Gestational exposure to ozone results in hepatic and systemic metabolic perturbations in male rat offspring. US DOHaD, Chapel Hill, NC, October 01 - 02, 2018.
Impact/Purpose:
This study aims to identify factors related to disruption of metabolism in rats on GD21 and postnatal day (PND) 45 in our model of growth restriction.
Description:
Intrauterine growth restriction is correlated with metabolic disease later in life. In our previous studies, we have found that exposure to ozone during implantation [gestational days (GD) 5 and 6] in rats resulted in growth restriction. This study aims to identify factors related to disruption of metabolism in rats on GD21 and postnatal day (PND) 45 in our model of growth restriction. Two cohorts of pregnant Long-Evans rats were exposed to filtered air or ozone (0.8 ppm) for four hours on GD5 and 6. Cohort one male fetuses were collected on GD21 to assess metabolic endpoints in the amniotic fluid and fetal liver. Cohort two male offspring were weaned onto a low-fat diet and had no interventions until PND45. Serum was collected for metabolic and hormonal assays and liver portions were collected for qPCR. T-tests were done within each time-point between offspring from air-exposed dams (air-offspring) and offspring from ozone-exposed dams (O3-offspring). Amniotic fluid from ozone exposed dams had lower leptin and insulin, and higher free fatty acid levels when compared to that of control dams (p<0.05). Livers collected from GD21 O3-offspring showed lower triglycerides, cholesterol, and glucose when compared to air-offspring (p<0.05). Fetal liver qPCR from GD21 O3-offspring demonstrated higher expression of the lipogeneic genes, Fasn, Acaca1 and Xbp1 (p<0.05). Serum collected from PND45 O3-offspring had higher leptin and insulin when compared to air-offspring (p<0.01). Hepatic glucose and total protein in O3-offspring were higher than air-offspring controls (p<0.05). Liver qPCR for PND45 offspring showed reduced expression of Fasn, Acaca1 and Xbp1 in O3-offspring (p<0.05). These results show that at GD21, the growth restricted O3-offspring have a disrupted metabolic phenotype suggestive of reduced nutritional resources in utero. Comparatively, O3-offspring reverse these changes in the opposite direction in adolescence, indicating continued metabolic perturbation. (Abstract does not reflect US EPA policy)