Maternal exposure to air pollution is increasingly linked, from an epidemiological standpoint, to adverse pregnancy outcomes such as preterm birth and low birth weight. Among the emerging pollutants are cerium dioxide nanoparticles, or nanoceria, which are used as catalytic additives in diesel fuels and cigarettes and subsequently released into the environment. Owing to their high surface-to-volume ratio and reactivity, these nanoparticles develop a surface coating during combustion that can incorporate other fuel-derived compounds. This is the case for benzo[a]pyrene, a polycyclic aromatic hydrocarbon recognized as carcinogenic, mutagenic, and toxic to reproduction, which raises the question of the combined effect of these two pollutants on human health.
To more closely mimic real-world environmental conditions, the authors produced benzo[a]pyrene-coated cerium dioxide nanoparticles and then exposed primary human trophoblasts and chorionic villi. The placenta, a complex transient organ, mediates maternal–fetal exchange and also has an endocrine function. Its functional unit, the chorionic villus, is covered by the syncytiotrophoblast, a multinucleated layer renewed through the fusion of the underlying villous cytotrophoblasts. In particular, the researchers assessed the activation of the aryl hydrocarbon receptor (AhR) pathway, trophoblast differentiation capacity, syncytium formation, mitochondrial phenotype and function, and placental steroidogenesis.
The benzo[a]pyrene-coated nanoparticles activated the AhR pathway and promoted trophoblast differentiation and syncytium formation, with effects distinct from those of benzo[a]pyrene or nanoparticles alone, or from their unbound mixture. Notably, the lowest dose exerted the most pronounced effect on differentiation and AhR activation: internalization analysis showed that this result was not due to greater cellular uptake but to improved bioavailability, with bioavailability proving more determinant than absolute intracellular load. The team further confirmed that internalization occurred through a lipid raft-dependent pathway. Uncoated nanoparticles alone disrupted mitochondrial homeostasis and altered placental steroidogenesis, increasing estrone levels and decreasing dehydroepiandrosterone levels, with effects dependent on placental sex. Whereas individual exposures had no detectable impact on cellular respiration, parallel co-exposure led to a slight but significant reduction in basal respiration.
This work indicates that cerium dioxide nanoparticles can modulate the biological effects of benzo[a]pyrene in the human placenta by influencing trophoblast differentiation and disrupting mitochondrial homeostasis and steroid production. The authors emphasize the importance of accounting for nanoparticle-bound pollutants in exposome studies, as these forms may exhibit bioavailability, persistence, and metabolic impact distinct from those of free pollutants, with potential consequences for pregnancy outcomes in polluted environments.