Prenatal exposure to air pollution affects autophagy, senescence and remodelling proteins in cord blood

Abstract

Background: Air pollution increases inflammation and reactive oxygen species that can induce autophagy, thereby leading to airway inflammation and remodelling. However, it is unclear whether prenatal air pollution may impact proteins involved in autophagy. The objectives of the present study were to investigate the associations of prenatal air pollution with proteins indicative of autophagy, senescence and remodelling in infants. Methods: We included 387 healthy term newborns from the BILD cohort study and measured 11 proteins: interleukin (IL)-1β, IL-8, matrix metallopeptidase (MMP)-3, MMP-9, platelet-derived growth factor (PDGF)-AA, transforming growth factor-β (TGF-β), sirtuin-1, p62, LC3B, tumour necrosis factor-α (TNF-α), and Beclin-1 in cord blood serum and plasma. We assessed the association of whole pregnancy residential exposure to nitrogen dioxide (NO2) and particulate matter (PM10) with protein levels using multivariable Tobit regression models. We performed unsupervised hierarchical clustering based on protein concentrations with a network construction of identified clusters. Results: Our results indicate that NO2 exposure during pregnancy can increase Beclin-1, a pivotal initiator of autophagy. Additionally, elevated NO2 exposure was correlated with a reduction in IL-8 levels. Unsupervised hierarchical clustering of all measured proteins gave four distinct clusters with similar protein expression profiles. When analysing the clusters’ clinical and exposure characteristics, significant differences were observed in NO2 and PM10 exposure during pregnancy. Network analysis revealed distinct protein–protein correlation patterns among clusters. Conclusions: Our findings in healthy term newborns showed that prenatal air pollution exposure is associated with alterations in levels of autophagy-related proteins. For the first time, we identified four distinct clusters of newborns, suggesting that there are different air pollution response patterns in a healthy population.