Exposure to environmental pollutants during pregnancy may increase the risk of asthma for as many as three consecutive generations, according to new research. The study is published ahead of print in the American Journal of Physiology -- Lung Cellular and Molecular Physiology.

Researchers studied three generations of mice born to mothers that were exposed to either diesel exhaust particles or urban air particle concentrate during pregnancy. The research team compared cells from the lungs of the first, second and third generations of offspring to three generations of control offspring that were not exposed to the pollutants. All generations descended from mothers exposed to diesel exhaust particles had an abnormal increase in a type of immune cell, a common marker for allergy. Offspring of pollutant-exposed ancestors also showed elevated levels of interleukin proteins that are involved in regulating the immune system, which are a marker of asthma risk. However, the increase was more prominent in the first and second generations, suggesting that inherited risk factors lessen in further removed generations.

Environmental pollutant exposure before birth caused epigenetic changes in the offspring's DNA that affect how genetic code is used (DNA methylation). The researchers found that atypical DNA methylation led to transgenerational asthma risk due to abnormal changes in a type of immune cell called dendritic cells. Dendritic cells play a key role in the development of asthma in early life.

Seeing the changes in DNA methylation and gene expression that affect the health of future generations (epigenetic transgenerational inheritance) may help doctors start to recognize asthma as not only an inflammatory disease but "to a large extent, an epigenetic disease," explained Alexey Fedulov, corresponding researcher on the study. "This approach may allow entirely new therapeutic strategies."