Pilot Projects

Project Title: In Utero Exposure to Allergen and Diesel: Transgenerational (Grandparental) Effects on Asthma-Like Outcomes in Mice

Co-Principal Investigators: Jinming Liu, Ph.D. (Dept. of Medicine) and Rachel Miller, M.D. (CEHNM)

Year: 2006
Award Amount: $25,000

Summary. Air toxics, such as indoor mold Aspergillus fumigatus (A. fumigatus) and diesel exhaust particles, have significant effects on airway allergic diseases, including asthma. Recent evidence suggests that the onset of asthma may be modulated by intrauterine environmental exposures. While this issue has been somewhat controversial in the literature, Dr. Miller's laboratory has generated, in both molecular biological studies with human participants, and in animal models, more definitive evidence of this occurrence. Three very recent events suggested that a study to determine whether the toxic effects of environmental exposures can reach the third generation of offspring would be of interest. First, Gilliland and colleagues from the Children's Health Study reported this past year that grandmaternal smoking during pregnancy may increase the risk of asthma in grandchildren regardless of the presence of maternal smoking. In addition, at both the NIEHS-sponsored Fetal Basis of Adult Disease Grantee Meeting in November of 2005 and the National Academy of Sciences (in collaboration with NIEHS)-sponsored Committee on Emerging Issues and Data on Environmental Contaminants, Early Life Exposure Workshop Meeting in February of 2006, transgenerational effects of environmental exposures were listed as future NIEHS directions/expectations.

In this Pilot Project, investigators will determine whether in utero exposure to A. fumigatus and/or diesel modulates the risk for asthma through the third generation of offspring. By employing an intrauterine A. fumigatus sensitization mouse model recently developed in Dr. Miller's laboratory, the effects of A. fumigatus, in combination with diesel exposure, on the asthma-like outcomes in third generation mice (i.e., elevated IgE level, increased airway hyperreactivity) will be determined when only the first generation (grandmother) is exposed. The planned studies will reveal whether airborne environmental exposures can affect asthma risk for multiple generations. Data acquired here will be used in future NIH grant application proposing to study the underlying mechanisms of transgenerational effects of environmental air toxic exposures.

Results & Outcomes. In progress (no publications to date).