Sex-Specific Metabolic Alterations In Offspring Of Mice Exposed Prenatally To Particulate Matter (Pm) From Petrodiesel (Pd) Combustion

Epidemiological studies report that exposure of expectant mothers to outdoor air pollution correlates with an increased risk of obesity, insulin resistance (IR) and earlier onset of type 2 diabetes mellitus in her offspring. To test the hypothesis that prenatal exposure to PM from PD combustion will lead to alterations in weight (WT) gain and insulin sensitivity, pregnant C57BL/6J mice were exposed daily to <10% ethanol (control, CON) or to ~80 ug of PM suspended in <10% ethanol, mimicking daily ambient exposure, via oropharyngeal aspiration from gestational day 9‐17 and allowed to deliver. Mice were fed standard chow after weaning. Weekly body WT, food intake (FI), bi‐weekly fasting glucose levels were measured for 44 wks. While FI was similar between CON and treated groups, female offspring (F) of mothers exposed to PD gained less WT than CON (p<0.001) whereas male offspring (M) began gaining more WT than CON after ~24 wks of age. M (n=10) were also hyperinsulinemic and insulin resistant (homeostatic model assessment of IR, HOMA‐IR) compared to CON (n=3) at 24 wks (1.8±0.2 vs 0.9±0.09 ng/ml; HOMA‐IR 15±2 vs. 7±1, respectively; p<0.05, mean±SE) despite a similar degree of fasting glycemia (135±5 vs 137±5 mg/dl). In contrast, F remained normoglycemic with no difference in HOMA‐IR between CON (n=4) and PD‐exposed (n=9). These data suggest that prenatal exposure to air pollution particulates from PD combustion has different metabolic effects in M compared to F that portend differential risk for metabolic dysfunction and may influence future reproductive capacity. (Support: UVM Transportation Research Center Project #026904).