Adverse Effects of Carbon Black Nanoparticles on Maternal and Fetal Lungs in Pregnant Mice: Insights From a Metabolomics Perspective

ABSTRACT

Previous studies have linked prenatal exposure to carbon black nanoparticles (CBNPs), a key constituent of air pollution and tobacco smoke, to respiratory abnormalities. However, the distinct impacts of particle size on the maternal‐fetal lung axis remain poorly understood. This study investigated the maternal‐to‐fetal lung toxicological effects and metabolic shifts following exposure to 30 nm (CBNP30) and 120 nm (CBNP120) particles using a high‐dose mechanistic exposure model. In maternal lungs, histological analysis (H&E and Masson staining) revealed severe inflammatory infiltration and significant fibrotic injury for both sizes, with CBNP120 inducing more pronounced damage. Dark‐field hyperspectral imaging confirmed the transplacental transfer and presence of both CBNP sizes within fetal lung tissues. Notably, fetal lungs did not display overt histological injury. However, significant elevations in oxidative stress and inflammatory markers (mRNA and protein) were observed, indicating clear molecular perturbation. Chemical Isotope Labeling LC–MS further identified size‐specific metabolic disruption, with CBNP120 eliciting more extensive changes in the fetal metabolome. Specifically, CBNP30 primarily affected histidine metabolism in both maternal and fetal lungs, whereas CBNP120 disrupted butanoate and arachidonic acid pathways. These metabolic shifts, supported by altered enzyme expression, suggest that profound biochemical disturbances may occur in the fetus even in the absence of observable morphological damage. This study clarifies the distinction between maternal structural injury and fetal molecular dysfunction, providing critical insights for interventions against air pollution‐related neonatal health risks.