Adverse neurodevelopment in children associated with prenatal exposure to fine particulate matter (PM 2.5 ) - Possible roles of polycyclic aromatic hydrocarbons (PAHs) and mechanisms involved.

Prenatal exposure to ambient fine particles (PM _2.5 ) and polycyclic aromatic hydrocarbons (PAHs) has been associated with adverse birth outcomes including neurodevelopmental effects with cognitive and/or behavioral implications in early childhood. As a background we first briefly summarize human studies on PM _2.5 and PAHs associated with adverse birth outcomes and modified neurodevelopment. Next, we add more specific information from animal studies and in vitro studies and elucidate possible biological mechanisms. More specifically we focus on the potential role of PAHs attached to PM _2.5 and explore whether effects of these compounds may arise from disturbance of placental function or more directly by interfering with neurodevelopmental processes in the fetal brain. Possible molecular initiating events (MIEs) include interactions with cellular receptors such as the aryl hydrocarbon receptor (AhR), beta-adrenergic receptors (βAR) and transient receptor potential (TRP)-channels resulting in altered gene expression. MIE linked to the binding of PAHs to cytochrome P450 (CYP) enzymes and formation of reactive electrophilic metabolites are likely less important. The experimental animal and in vitro studies support the epidemiological findings and suggest steps involved in mechanistic pathways explaining the associations. An overall evaluation of the doses/concentrations used in experimental studies combined with the mechanistic understanding further supports the hypothesis that prenatal PAHs exposure may cause adverse outcomes (AOs) linked to human neurodevelopment. Several MIEs will likely occur simultaneously in various cells/tissues involving several key events (KEs) which relative importance will depend on dose, time, tissue, genetics, other environmental factors, and neurodevelopmental endpoint in study.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)