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Gestational E-Cigarette Exposure, Transgenerational Asthma, and the Germ Cell Epigenetic Memory

Institution: LA Biomedical Research Institute at Harbor-UCLA Medical Center
Investigator(s): Virender Rehan,
Award Cycle: 2019 (Cycle 29) Grant #: T29IR0737 Award: $1,048,215
Subject Area: Pulmonary Disease
Award Type: High Impact Research Project Award

Initial Award Abstract
There has been a sharp rise in vaping, largely the result of the perception among users that vaping is essentially harmless because it does not contain smoke. The result is increased exposure of developing fetuses to potential harm not just from nicotine, but also from the flavorings in the inhaled vapors. Thus far, there has been little few systematic investigations on the potential adverse health effects of vaping. Our preliminary data in animals show that the effects of nicotine can have harmful effects to subsequent generations of offspring, even though they are never exposed to nicotine. In a well-established animal model, we exposed pregnant dams to nicotine, and found that not only did their offspring develop asthma at a significantly greater rate compared to controls who were naive to nicotine, but the subsequent generation of offspring were at significantly increased risk as well, despite never having been exposed to nicotine at all. These data led us to wonder whether exposure to vaping via e-cigarettes (e-cigs) might produce the same adverse health effects as well. Here we propose to address questions that naturally arise from these provocative data: Can adverse effects of nicotine delivered by e-cigs impact subsequent generations? What is the role of flavorings in e-cigs? How do e-cigs impact the epigenome of germ cells (eggs and sperm)? How does that influence the development of lung cells (which differentiate from germ cells)? Are they normal, or abnormal? Our studies will address these questions using established models and experienced collaborators. Specifically, we propose to investigate whether vaping effects can be transmitted across generations, and determine the relative impact of inhaled nicotine and flavorings. Furthermore, we will determine the effects of vaping on germ cell viability and epigenetic memory. Our investigation will advance the understanding of how adverse effects of vaping are transmitted to future generations, and will not just inform public policy makers, but will arm them with objective evidence as they work to protect our society and our offspring from the harmful effects of vaping.