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

J Am Heart Assoc. 2018 Dec 18;7(24):e010797. doi: 10.1161/JAHA.118.010797.


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.

Keywords: calcium; cardiovascular function; inflammation; myocyte; particulate matter; preconception.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Calcium Signaling / drug effects
  • Epigenesis, Genetic / drug effects
  • Female
  • Gene Expression Regulation, Developmental / drug effects
  • Inflammation Mediators / metabolism
  • Inhalation Exposure / adverse effects*
  • Male
  • Maternal Exposure / adverse effects*
  • Mice
  • Myocardial Contraction / drug effects
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism
  • Oxidative Stress / drug effects
  • Particle Size
  • Particulate Matter / toxicity*
  • Paternal Exposure / adverse effects*
  • Preconception Injuries / chemically induced*
  • Preconception Injuries / genetics
  • Preconception Injuries / metabolism
  • Preconception Injuries / physiopathology
  • Risk Assessment
  • Risk Factors
  • Sex Factors
  • Stroke Volume / drug effects
  • Ventricular Dysfunction, Left / chemically induced*
  • Ventricular Dysfunction, Left / genetics
  • Ventricular Dysfunction, Left / metabolism
  • Ventricular Dysfunction, Left / physiopathology
  • Ventricular Function, Left / drug effects*
  • Ventricular Function, Left / genetics


  • Inflammation Mediators
  • Particulate Matter