Translocation of combustion-derived particles from mother to fetus

Abstract

Every single one of us is constantly exposed to polluted air, and this is not different for pregnant women. Considering the link between prenatal air pollution exposure and various adverse pregnancy and birth outcomes, the question arises if air polluting particles, of which it is known that the combustion-derived fraction is particularly harmful, can bypass the placenta to reach the fetal circulation and organs to exert possible toxic effects. A plausible yet controversial explanation comprises transplacental particle transfer from the mother’s lungs via maternal blood and through the placenta to the fetal circulation. In this regard, the overall objective of this dissertation is to unravel the ability of air polluting particles, with a focus on combustion-derived particles (CDPs), to reach the maternal-fetal circulation. The key messages of each chapter discussed in this dissertation are summarised in Table 1. First, we provide a systematic review of the existing literature on transplacental transfer and placental-fetal accumulation of combustion-derived (ultra)fine particles and nanoparticles (Chapter I). Here we conclude that (i) there is sufficient experimental evidence to support the idea that combustion-derived (ultra)fine particles and engineered nanoparticles are able to bypass the placenta and reach the fetal circulation as observed for all applied models, irrespective of species origin (i.e., rodent, rabbit or human) or complexity (i.e., in vitro, ex vivo or in vivo), (ii) the majority of available studies is based on (nano)particles not related to combustion processes despite the demonstrated toxicity of CDPs, (iii) particle size, particle material, dose, particle dissolution, surface composition and gestational stage of the model influence maternal-fetal translocation and (iv) no simple, standardised method for particle detection and/or quantification in biological samples is available to date. Given the established link between prenatal exposure to combustion-derived air pollution and adverse birth outcomes, combined with the limited knowledge on their transplacental transfer, the possibility of a direct fetal exposure needs to be urgently investigated. In this dissertation, we substantiate the pathway following direct effects on fetal development, caused by transplacental particle translocation, by showing that CDPs, more specifically black carbon (BC) particles, can reach the human placenta (Chapter II) under real-life exposure conditions. Ex vivo placental perfusion with diesel exhaust particles disclosed a preferential accumulation in the syncytiotrophoblast layer and an ability to overcome this layer to reach the fetal capillaries (Chapter III). The presence of CDPs in human cord blood and fetal tissues from electively terminated normally progressing pregnancies (Chapter IV) and gestationally exposed rabbits (Chapter V) further confirmed their transfer to the fetal circulation under real-life and controlled exposure conditions, respectively. These findings show the ubiquity of this environmental pollutant and prove that ambient CDPs can be transported directly to the next generation, which may be, at least partially, responsible for the observed detrimental health effects from early life onwards. Our findings support direct exposure pathways, yet indirect effects should be investigated in parallel to improve the understanding of how prenatal air pollution exposure may affect fetal development and health in early life. It should be noted that these results were observed in population-based studies under real-life exposure conditions, with levels below the current European air quality standards, (Chapters II and IV) and were unequivocally confirmed in a controlled exposure setting (Chapters III and V). These substantial and socially relevant findings should increase the pressure on government and individuals to pursue action to reduce current air pollution levels even further and, with this, protect the most vulnerable in our society, namely pregnant women.