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

Abstract

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...

Cardiovascular adaptations to particle inhalation exposure: molecular mechanisms of the toxicology

“…The interactions represent direct, validated experimental associations between genes that were increased (red), decreased (green), or found to have a diverse expression profile (yellow) following exposures. All abbreviations are defined in GLOSSARY. in 3-mo-old progeny (148). Inflammatory and oxidative pathways are thereby activated, resulting in increased IL᎑6, IL᎑15, NF-B, and CRP, along with elevated fibrosis (Col3a1), similar to the results found in many direct exposure studies.…”

“…This further suggests the ability of gestational PM exposure to induce global epigenetic remodeling through transcriptional activation of acetylated regions in offspring. Supporting these findings, multiple additional studies have reported a cardiac hypertrophic/fibrotic phenotype, cardiac functional changes, and epigenetic reprogramming in early development due to gestational PM exposure (148,150,169). Preconception exposure in both parents to PM 2.5 resulted in progeny with decreased ejection fraction, fractional shortening, and cardiomyocyte contractility at 12 wk of age (148).…”

“…PM 2 exposure results in activation of oxidative and inflammatory pathways, as has been described in the previous sections. Preconception toxicant exposure predisposes future offspring to the development of cardiac dysfunction (148). PM 2.5 preconception exposure in both parents decreases ejection fraction, fractional shortening, and cardiomyocyte contractility Fig.…”

Parental PM2.5 exposure changes Th17/Treg cells in offspring, is associated with the elevation of blood pressure

“…More importantly, maternal exposure to ambient PM 2.5 during the third trimester of pregnancy was associated with elevated blood pressure in children aged 3 to 9 years 24 . Exposure to PM 2.5 during preconception, 25 in utero, and early life development in mice increased cardiac abnormalities or aggravated susceptibility to heart failure 26 . Although these studies found that maternal exposure to ambient PM 2.5 was associated with offspring hypertension, the effects of parental PM 2.5 exposure on susceptibility of offspring to air pollution was lacking.…”

“…23 More importantly, maternal exposure to ambient PM 2.5 during the third trimester of pregnancy was associated with elevated blood pressure in children aged 3 to 9 years. 24 Exposure to PM 2.5 during preconception, 25 in utero, and early life development in mice increased cardiac abnormalities or aggravated susceptibility to heart…”