In utero exposure to diesel exhaust is associated with alterations in neonatal cardiomyocyte transcription, DNA methylation and metabolic perturbation

Jamie M. Goodson,
James W. MacDonald,
Theo K. Bammler,
Wei-Ming Chien and
Michael T. ChinEmail author View ORCID ID profile

Particle and Fibre Toxicology201916:17

https://doi.org/10.1186/s12989-019-0301-9

Received: 25 October 2018
Accepted: 3 April 2019
Published: 11 April 2019

Abstract

Background

Developmental exposure to particulate matter air pollution is harmful to cardiovascular health, but the mechanisms by which this exposure mediates susceptibility to heart disease is poorly understood. We have previously shown, in a mouse model, that gestational exposure to diesel exhaust (DE) results in increased cardiac hypertrophy, fibrosis and susceptibility to heart failure in the adult offspring following transverse aortic constriction.

Results

In this study, we have analyzed gene expression in neonatal cardiomyocytes after gestational exposure by RNA-sequencing and have identified 300 genes that are dysregulated, including many involved in cardiac metabolism. We subsequently determined that these cardiomyocytes exhibit reduced metabolic activity as measured by Seahorse extracellular flux analysis. We also surveyed for modifications in DNA methylation at global regulatory regions using reduced representation bisulfite sequencing and found hypomethylation of DNA in neonatal cardiomyocytes isolated from in utero DE exposed neonates.

Conclusion

We have demonstrated that in utero exposure to diesel exhaust alters the neonatal cardiomyocyte transcriptional and epigenetic landscapes, as well as the metabolic capability of these cells. Understanding how exposure alters the developing heart through dysregulation of gene expression, metabolism and DNA methylation is vital for identifying therapeutic interventions for air pollution-related heart failure.