Student Presenter: Jeremy Adelstein Booth Number: 1 Research Mentor: Loren Wold Project Title: Exposure to PM2.5 Preconception Primes Adult Cardiac Dysfunction

Previous studies have demonstrated that particulate matter, or ambient particles less than 2.5 μm (PM2.5) in diameter, exposure during both in utero and postnatal developmental periods triggers electrical remodeling and cardiac dysfunction during adulthood. This shows that PM2.5 can reprogram hearts that are developing in the gestational period. Despite this evidence, the cardiac effects from pregestational particulate matter exposure remain inconclusive. This study was carried out to further investigate the potential priming effects of preconception exposure of PM2.5 on global cardiac dysfunction at adulthood. METHODS: Male and female FVB mice were exposed separately to either filtered air (FA) or PM2.5 at a concentration of ~ 51.69 μg/m3 for 6 h/day, 7 days/wk (consistent with exposure in a large metropolitan city) for 3 months. Mice were then cross bred in two groups: (1) FAm X FAf (both parents were FA exposed) and, (2) PMm X PMf (both parents were PM exposed). Offspring born to these crosses (FAFA and PMPM) were analyzed at 3 months of age for in vivo cardiac function via echocardiography, followed by in vitro cardiomyocyte functional analyses. RESULTS: Echocardiography identified increased LVEDd (3.97 ± 0.11 FAFA, 4.32 ± 0.10 PMPM, P=0.04) and LVESd (2.58 ± 0.13 FAFA, 2.93 ± 0.13 PMPM, P=0.1) dimensions in mice born to PMm X PMf parents. Morphological alterations were associated with lower systolic function indicated by reduced fractional shortening % (35.13% ± 1.67 FAxFA, 29.29% ± 1.38 PMxPM, P=0.03) in mice born to PMm X PMf parents. Cardiomyocytes isolated from PMPM offspring showed reduced peak shortening %PS (13.21% ± 0.67 FAFA, 10.15% ± 0.68 PMPM, P=0.002). -dL/dt was significantly increased (-5.38 ± 0.28 FAFA, -4.32 ± 0.33 PMPM, P=0.01) whereas +dL/dt remained unchanged between the groups. CONCLUSION: Similar to our previous study involving in utero exposure, preconception exposure to PM2.5 at realistic concentrations results in adult cardiac dysfunction. These results suggest that abnormalities in developmental potential are not limited to prenatal or postnatal period but are also determined prior to conception. Student Presenter: Richa Agrawal