Exposure to environmental pollution, such as diesel exhaust or concentrated urban air particles, during pregnancy could increase a child’s risk of developing asthma via epigenetic mechanisms. Recent research in the Journal of Physiology – Lung Cellular and Molecular Physiology suggests that this allergic susceptibility might even be epigenetically passed down for several generations.
Asthma forms as a result of the complex interaction between someone’s genes, epigenetic marks, and the environment. Epigenetics, the study of how chemical tags impact the expression of genes, is coming more into focus as researchers attempt to understand this widespread respiratory condition and its origins.
Previous research has uncovered an association between inhaling diesel exhaust fumes and notable epigenetic changes – which can affect around 400 genes. Other studies link birth season and allergy risk and uncover new gene targets for creating drugs to combat allergic diseases and reduce allergic responses.
In this study, researchers from Harvard T.H. Chan School of Public Health, along with Bringham and Women’s Hospital, expanded on their prior observations that maternal particle or allergen exposure can be connected to increased asthma onset risk in the immediate progeny, known as the F1 generation. Interestingly, their new research supports the notion that it actually extends all the way to the third generation (F3), even though the effect is not as strong.
Using a mouse model, they found that pregnant mothers exposed to pollutants increased the risk of asthma in their children, grandchildren, and great-grandchildren. The scientists assessed key immune cells known as dendritic cells from within the mice’s lungs, since these special cells are thought to be critical in early-life onset of asthma and maternal transmission of asthma risk.
All three generations of offspring exposed to diesel exhaust had an abnormal boost in dendritic cells, used as a common marker for allergy. Descendants of pollutant-exposed mothers also had increased levels of interleukin proteins that are linked to immune system regulation.
They assessed the pattern of DNA methylation, a common epigenetic mechanism defined as the addition of a methyl mark which often suppresses the expression of genes, in dendritic cells of each generation. After purifying the dendritic cells and isolating the DNA, the researchers used enhanced reduced representation bisulfite sequencing (eRRBS).
“Our methylome analysis suggests that the transmission is associated with aberrant DNA chromatin dynamics.”,” the team reported. “Increased asthma susceptibility after a single maternal exposure to [diesel exhaust particles] or [concentrated urban air particles] transmits risk to F1, F2, and, to a lesser extent, F3 generations. This was associated with altered methylation of promoters of genes associated with lung development, IL-4 signaling, and
Transgenerational epigenetic inheritance is a highly debated topic that certainly requires more research. An effect must be observed in generations that were not exposed to the triggering stimulus – in this case, pollution – in order to qualify as transgenerational. Recent research has suggested that mothers exposed to lead may influence DNA methylation patterns of her children and grandchildren. Other studies, however, show that nutrition “memory” does not epigenetically persist to great grandchildren.
To further substantiate the epigenetic effect the group observed, the researchers treated a subset of immediate offspring with a DNMT inhibitor, which inhibits the epigenetic enzyme that catalyzes DNA methylation. This drug can modify DNA methylation in the epigenome and could potentially reduce the transmission of asthma susceptibility. Indeed, they found that injecting the F1 generation with a DNMT inhibitor called decitabine for three days immediately before mating was able to attenuate the asthma risk in grandchildren and great-grandchildren.
Expanding our knowledge of epigenetic origins of asthma may lead to novel prevention and treatment strategies. Not only is asthma an inflammatory disease but it is an epigenetic disease as well, explained corresponding researcher Alexey Fedulov. According to him, “This approach may allow entirely new therapeutic strategies.”
Source: Gregory, D.J. et al. (2017). Transgenerational transmission of asthma risk after exposure to environmental particles during pregnancy. American Journal of Physiology – Lung Cellular and Molecular Physiology, 313(2): L395-L405.
Reference: The American Physiological Society. Environmental Pollution Exposure during Pregnancy Increases Asthma Risk for Three Generations. The American Physiological Society Press Release. 17 May 2017. Web.