Maternal exposure to polystyrene nanoplastics induces sex-specific kidney injury in offspring

Maternal exposure to polystyrene nanoplastics (PS-NPs) during pregnancy and lactation has been linked to adverse effects on offspring kidney development, with sex-specific outcomes. This study investigated the impact of maternal PS-NPs exposure on kidney weight, histology, transcriptomics, and functional pathways in offspring mice. Offspring exposed to PS-NPs exhibited significantly lower body weight (P < 0.05) and an increased kidney-to-body weight ratio (P < 0.05), particularly in males. Histological analysis revealed a reduction in glomerular number in PS-NP-treated groups. Transcriptome profiling identified 758 differentially expressed genes (DEGs) in male and 101 DEGs in female offspring, with males showing a more pronounced alteration in gene expression. KEGG pathway enrichment highlighted disruptions in immune response, cell cycle regulation, and metabolism, with males exhibiting more extensive pathway changes than females. Additionally, PS-NPs exposure increased renal fibrosis (P < 0.05), with molecular analyses confirming sex-specific gene expression patterns linked to fibrosis and apoptosis. Immunohistochemical analysis revealed enhanced macrophage infiltration and cleaved caspase-3 expression, indicating heightened immune and apoptotic responses in males. Further investigation identified small molecules BI-D1870 and Resatorvid as potential therapeutic agents, reducing fibrosis, inflammation, and apoptosis in male and female offspring, respectively. These findings demonstrate that maternal PS-NPs exposure induces sex-specific kidney injury in offspring, disrupting key biological processes and pathways. The study underscores the need for targeted therapeutic interventions to mitigate these effects and highlights potential compounds for future treatment.