Background Particulate matter (particles < 2.5 μm [ PM 2.5 ]) exposure during the in utero and postnatal developmental periods causes cardiac dysfunction during adulthood. Here, we investigated the potential priming effects of preconception exposure of PM 2.5 on cardiac function in adult offspring. Methods and Results Male and female friend leukemia virus b (FVB) mice were exposed to either filtered air ( FA ) or PM 2.5 at an average concentration of 38.58 μg/m 3 for 6 hours/day, 5 days/week for 3 months. Mice were then crossbred into 2 groups: (1) FA male × FA female (both parents were exposed to FA preconception) and, (2) PM 2.5male × PM 2.5female (both parents were exposed to PM 2.5 preconception). Male offspring were divided: (1) preconception FA (offspring born to FA exposed parents) and, (2) preconception PM 2.5 (offspring born to PM 2.5 exposed parents) and analyzed at 3 months of age. Echocardiography identified increased left ventricular end systolic volume and reduced posterior wall thickness, reduced %fractional shortening and %ejection fraction in preconception PM 2.5 offspring. Cardiomyocytes isolated from preconception PM 2.5 offspring showed reduced %peak shortening, −dL/dT, TPS 90 and slower calcium reuptake (tau). Gene and protein expression revealed modifications in markers of inflammation ( IL ‐6, IL ‐15, TNF α, NF қB, CRP , CD 26E, CD 26P, intercellular adhesion molecule 1, and monocyte chemoattractant protein‐1) profibrosis (collagen type III alpha 1 chain), oxidative stress ( NOS 2), antioxidants (Nrf2, SOD , catalase), Ca 2+ regulatory proteins ( SERCA 2a, p‐ PLN , NCX ), and epigenetic regulators (Dnmt1, Dnmt3a, Dnmt3b, Sirt1, and Sirt2) in preconception PM 2.5 offspring. Conclusions Preconception exposure to PM 2.5 results in global cardiac dysfunction in adult offspring, suggesting that abnormalities during development are not limit...

Objective Exposure of fine particulate matter (PM2.5) to pregnant dams has been shown to be strongly associated with adverse cardiovascular outcomes in offspring at adulthood, however, effects evident during neonatal periods are unclear. We designed this study to examine cardiac function of neonatal mice (14 days old) exposed to in utero PM2.5. Methods Pregnant FVB female mice were exposed either to filtered air (FA) or PM2.5 at an average concentration of 91.78 μg/m3 for 6h/day, 5 days/wk (similar to exposure in a large industrial area) throughout the gestation period (20 days). After birth, animals were analyzed at day 14 of life. Results Fourteen day old mice exposed to PM2.5 during in utero period demonstrated decreased fractional shortening (%FS, 41.1±1.2% FA, 33.7±1.2% PM2.5, p<0.01) and LVEDd (2.87±0.08 mm FA, 2.58±0.07 mm PM2.5, p<0.05) compared to FA exposed mice. Contractile kinetics and calcium transients in isolated cardiomyocytes from PM2.5 exposed mice illustrated reduced peak shortening (%PS, 16.7±0.5% FA, 14.7±0.4% PM2.5, p<0.01), negative contractile velocity (- dL/dT, -6.91±0.3 μm/s FA, -5.46±0.2 μm/s PM2.5, p<0.001), increased time to relaxation 90% (TR90, 0.07±0.003 s FA, 0.08±0.004 s PM2.5, p<0.05), decreased calcium transient amplitude (Δ340/380, 33.8±3.4 FA, 29.5±2.8 PM2.5) and slower fluorescence decay rate (τ, 0.72±0.1 s FA, 1.16±0.15 s PM2.5, p<0.05). Immunoblotting studies demonstrated alterations in expression of Ca2+ handling proteins- SERCA-2A, p-PLN, NCX and CaV1.2 in hearts of 14 day old in utero PM2.5 exposed mice compared to FA exposed hearts. Conclusion PM2.5 exposure during the critical in utero period adversely affects the developing mouse fetus leading to functional cardiac changes that were evident during the very early (14 days) stages of adolescence. These data demonstrated that exposure to PM2.5 during the gestation period significantly impacts cardiovascular outcomes early in life.

ObjectivePrevious 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 during the gestational period. Despite this evidence, cardiac effects from pre‐gestational particulate matter exposure remain inconclusive. This study was performed to further investigate the potential priming effects of preconception exposure of PM2.5 on global cardiac dysfunction at adulthood.METHODSMale and female FVB mice were exposed separately to either filtered air (FA) or PM2.5 at a concentration (within the annual average range of 15 μg/m3 according to the National Ambient Air Quality Standards (NAAQS)) for 3 months. Mice were then cross bred into 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 (PC FA and PC PM2.5) were analyzed at 3 months of age for in vivo cardiac function via echocardiography, followed by in vitro cardiomyocyte functional and molecular analyses.RESULTSEchocardiography identified increased LVESd (2.58 ± 0.13 PC FA, 2.93 ± 0.13 PC PM2.5, P=0.1) and reduced PWTs (1.70 ± 0.06 PC FA, 1.44 ± 0.08 PC PM2.5, P=0.05) dimensions in PC PM2.5‐exposed mice. Morphological alterations were associated with lower systolic function indicated by reduced fractional shortening % (35.09% ± 1.34 PC FA, 29.05% ± 1.25 PC PM2.5, P=0.03) and ejection fraction % (64.86% ± 1.76 PC FA, 56.27% ± 1.95 PC PM2.5, P=0.03) in PM2.5‐exposed mice. Cardiomyocytes isolated from PC PM2.5 mice showed reduced peak shortening %PS (12.93% ± 0.42 PC FA, 11.10% ± 0.41 PC PM2.5, P=0.002), −dL/dT (−10.60 ± 0.82 PC FA, −8.50 ± 0.60 PC PM2.5, P=0.05), TPS90 (0.08 ± 0.003 PC FA, 0.07 ± 0.002 PC PM2.5, P=0.05) and slower calcium reuptake (tau, 0.42±0.06 s FA, 0.67±0.09 s PC PM2.5, P=0.05). qPCR analyses revealed decreased MURC, MyBPC3 and increased Mypt1 expression and western blot analyses demonstrated modified NCX, SERCA and PLN expression in PC PM2.5‐exposed mice compared to PC FA‐exposed mice.CONCLUSIONSimilar to our previous study involving in utero exposure, preconception exposure to PC PM2.5 at real‐world concentrations results in adult cardiac dysfunction. These results suggest that abnormalities in developmental potential are not limited to prenatal or postnatal period but can also be determined prior to conception.Support or Funding InformationThis work is supported by funding from National Institutes of Health (RO1ES019923) to LEW.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.