Subclinical immunometabolic perturbations in the neonatal lung following maternal microplastic exposure in mice
Abstract
Maternal exposure to microplastics has raised concerns regarding early-life health effects, yet the molecular alterations preceding structural lung injury remain poorly defined. We investigated whether perinatal polystyrene microplastic (PS-MP) exposure is associated with inflammatory and metabolic changes in neonatal mouse lungs. Pregnant C57BL/6 mice received PS-MPs (100 or 1000 μg/L) in drinking water from gestation day 14 to postnatal day (PD) 14, corresponding to an estimated intake of approximately 16-160 μg/kg/day, within an environmentally relevant sub-mg/kg/day exposure range. Lung tissues were analyzed at PD7 and PD14 using cytokine assays, NF-κB assessment, histopathology, and untargeted metabolomics. High-dose exposure (1000 μg/L) was associated with enrichment of arachidonic and linoleic acid metabolism, reductions in cyclic AMP (cAMP)- and purine-associated metabolites, and decreased glutathione-related and acylcarnitine-associated features. Targeted biochemical analyses confirmed reduced pulmonary cAMP levels, increased GSSG concentrations, and decreased GSH/GSSG ratios following exposure. These alterations were accompanied by increased IL-1, IL-6, and TNF-α at both PD7 and PD14. NF-κB expression showed exposure-associated increases, although the statistical robustness was influenced by litter-level variability. Despite these changes, lung architecture and lung-to-body weight ratios remained preserved, and only modest, dose-specific growth reduction was…
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