Subclinical immunometabolic perturbations in the neonatal lung following maternal microplastic exposure in mice

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 observed. Collectively, these findings suggest that perinatal microplastic exposure is associated with early immunometabolic perturbations characterized by inflammatory activation, altered lipid metabolism, reduced pulmonary cAMP levels, and disrupted glutathione redox homeostasis despite preserved lung histoarchitecture.