Transgenerational transmission of asthma risk after exposure to environmental particles during pregnancy

American Journal of Physiology. Lung Cellular and Molecular Physiology
David J GregoryAlexey Fedulov

Abstract

Exposure to environmental particles during pregnancy increases asthma susceptibility of the offspring. We tested the hypothesis that this transmission continues to F2 and F3 generations and occurs via epigenetic mechanisms. We compared allergic susceptibility of three generations of BALB/c offspring after a single maternal exposure during pregnancy to diesel exhaust particles or concentrated urban air particles. After pregnant dams received intranasal instillations of particle suspensions or control, their F1, F2, and F3 offspring were tested in a low-dose ovalbumin protocol for sensitivity to allergic asthma. We found that the elevated susceptibility after maternal exposure to particles during pregnancy persists into F2 and, with lesser magnitude, into F3 generations. This was evident from elevated eosinophil counts in bronchoalveolar lavage (BAL) fluid, histopathological changes of allergic airway disease, and increased BAL levels of IL-5 and IL-13. We have previously shown that dendritic cells (DCs) can mediate transmission of risk upon adoptive transfer. Therefore, we used an enhanced reduced representation bisulfite sequencing protocol to quantify DNA methylation in DCs from each generation. Distinct methylation changes we...Continue Reading

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Citations

Nov 1, 2017·Expert Opinion on Drug Metabolism & Toxicology·Yanli ZhangLongquan Shao
Feb 2, 2019·Birth Defects Research·Kristal A Rychlik, Fenna C M Sillé
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Nov 17, 2019·Genes·Andrée-Anne Hudon Thibeault, Catherine Laprise
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Sep 30, 2021·American Journal of Physiology. Lung Cellular and Molecular Physiology·Qianghu TangZhen Zou
Nov 23, 2018·International Archives of Allergy and Immunology·Elizabeth Huiwen ThamLynette Pei-Chi Shek

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Methods Mentioned

BETA
bronchoalveolar
lavage
bronchoalveolar lavage
blood collection
ELISA
flow cytometry
methylation profiling
methylation sequencing
RRBS
Assay

Software Mentioned

Enrichr
DSS
Metacore
GeneGo Metacore
Prism
Methylkit
GeneGo

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