Effects of Atmospheric Pollution on Placental function and post-natal development – EPPAP

The DOHaD (Developmental Origins of Health and Disease) hypothesis states that exposure to exogenous stressors during the developmental period can alter fetal development and increase the risk of diseases in childhood and later. Alterations of epigenetic marks constitute one mechanism whereby these stressors could impact on health on the long term. So far, animal research has mostly focused on the impact of orally-absorbed contaminants. The effects of atmospheric pollutants have been little considered, while human exposure is widespread and epidemiological studies conducted by one of the consortium partners suggest that air pollution exposure during intra-uterine life can alter fœtal development and impact on birth outcomes. These human studies are however limited in terms of ability to highlight the underlying biological mechanisms and long-term consequences of such exposure.
The aim of the EPAPP project is to characterize the effects of traffic-related atmospheric pollution (diesel engine exhaust) on fetal and post-natal development in an animal model. We will expose daily pregnant and/or suckling female rabbits to diluted diesel engine exhaust using a device specifically designed for this purpose (MAPCEL mobile laboratory). The rabbit model is particularly pertinent due to anatomical and physiological features (size allowing the monitoring of fetal growth, nostril and airways size, placental structure and function…). The experimental approach will focus on embryo, placental function, fetal development, lactation, offspring health, gonadal development and fertility. The impact of traffic-related air pollution on embryo and placental gene expression will be studied using a transcriptomic approach. Moreover, placental epigenetic regulation and epigenetic alteration by atmospheric pollution will be analysed by MeDIP/Chip taking advantage of the design of a new specific rabbit promoter micro-array. The placenta methylome will be characterized in parallel in a human cohort in order to define epigenetic biomarkers of effect of diesel engine exhaust. More generally, a systematic comparison of results with those already obtained in humans on similar outcomes (fetal growth, placental function…) will be undertaken. Results are expected to have far-reaching implications in environmental health research, inhalation toxicology, DOHaD hypothesis and for public health and regulation of traffic-related pollutants.