Preconception Exposure to Fine Particulate Matter Leads to Cardiac Dysfunction in Adult Male Offspring

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/m³ 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), Ca²⁺ 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 limited to the prenatal or postnatal periods but can also be determined before conception.