Air pollution-induced placental alterations: an interplay of oxidative stress, epigenetics, and the aging phenotype?

According to the "Developmental Origins of Health and Disease" (DOHaD) concept, the early-life environment is a critical period for fetal programming. Given the epidemiological evidence that air pollution exposure during pregnancy adversely affects newborn outcomes such as birth weight and preterm birth, there is a need to pay attention to underlying modes of action to better understand not only these air pollution-induced early health effects but also its later-life consequences. In this review, we give an overview of air pollution-induced placental molecular alterations observed in the ENVIRONAGE birth cohort and evaluate the existing evidence. In general, we showed that prenatal exposure to air pollution is associated with nitrosative stress and epigenetic alterations in the placenta. Adversely affected CpG targets were involved in cellular processes including DNA repair, circadian rhythm, and energy metabolism. For miRNA expression, specific air pollution exposure windows were associated with altered miR-20a, miR-21, miR-146a, and miR-222 expression. Early-life aging markers including telomere(definition) length and mitochondrial DNA content are associated with air pollution exposure during pregnancy. Previously, we proposed the air pollution-induced telomere-mitochondrial aging hypothesis with a direct link between telomeres and mitochondria. Here, we extend this view with a potential co-interaction of different biological mechanisms on the level of placental oxidative stress, epigenetics, aging, and energy metabolism. Investigating the placenta is an opportunity for future research as it may help to understand the fundamental biology underpinning the DOHaD concept through the interactions between the underlying modes of action, prenatal environment, and disease risk in later life. To prevent lasting consequences from early-life exposures of air pollution, policy makers should get a basic understanding of biomolecular consequences and transgenerational risks.