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Transcriptomic Meta-Analysis Unveils Shared Neurodevelopmental Toxicity Pathways and Sex-Specific Transcriptional Signatures of Established Neurotoxicants and Polystyrene Nanoplastics as an Emerging Contaminant
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This meta-analysis compared gene expression patterns caused by nanoplastics with those from known brain-toxic chemicals like BPA. It found that polystyrene nanoplastics activate many of the same harmful pathways as established neurotoxicants, with some effects differing between males and females, suggesting plastic particles may pose similar risks to brain development.
Environmental contaminants exhibit heterogeneous neurotoxicity profiles, yet systematic comparisons between legacy neurotoxicants and emerging pollutants remain scarce. To address this gap, we implemented an integrative transcriptome meta-analysis framework that harmonized eight transcriptomic datasets spanning in vivo and in vitro neural models exposed to two legacy neurotoxicants (bisphenol A [BPA], 2, 2', 4, 4'-tetrabromodiphenyl ether [BDE-47]) and polystyrene nanoplastics (PSNPs) as an emerging contaminant. Our analysis revealed a substantial overlap (68% consistency) in differentially expressed genes (DEGs) between BPA and PSNPs, with shared enrichment in extracellular matrix disruption pathways (e.g., "fibronectin binding" and "collagen binding", p < 0.05). Network-based toxicogenomic mapping linked all three contaminants to six neurological disorders, with BPA showing the strongest associations with Hepatolenticular Degeneration. Crucially, a sex-stratified analysis uncovered male-specific transcriptional responses to BPA (e.g., lipid metabolism and immune response dysregulation), whereas female models showed no equivalent enrichment. This highlights the sex-specific transcriptional characteristics of BPA exposure. This study establishes a novel computational toxicology workflow that bridges legacy and emerging contaminant research, providing mechanistic insights for chemical prioritization and gender-specific risk assessment.
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Researchers chronically exposed male mice to polystyrene nanoplastics via drinking water for 17 months and performed transcriptomic analysis of brain tissue, finding significant upregulation of Alzheimer's, Parkinson's, and cardiovascular disease pathways—suggesting long-term nanoplastic exposure drives systemic molecular network reorganization well beyond the brain.
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Researchers reviewed how endocrine disruptors, particulate matter, and micro/nanoplastics cause sex-dependent neurotoxicity, finding that biological differences between male and female brains shape their vulnerability to these pollutants and that most prior toxicology studies have overlooked sex as a variable, leaving important knowledge gaps for public health policy.
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