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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\u2032, 4, 4\u2032-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., \u201cfibronectin binding\u201d and \u201ccollagen binding\u201d, p &lt; 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.<\/jats:p>","DOI":"10.3390\/toxics13080613","type":"journal-article","created":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T15:00:42Z","timestamp":1753196442000},"page":"613","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Transcriptomic Meta-Analysis Unveils Shared Neurodevelopmental Toxicity Pathways and Sex-Specific Transcriptional Signatures of Established Neurotoxicants and Polystyrene Nanoplastics as an Emerging Contaminant"],"prefix":"10.3390","volume":"13","author":[{"given":"Wenhao","family":"Wang","sequence":"first","affiliation":[{"name":"Shanxi Key Laboratory of Coal-Based Emerging Pollutant Identification and Risk Control, Research Center of Environment and Health, College of Environment and Resource, Shanxi University, Taiyuan 030006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutong","family":"Liu","sequence":"additional","affiliation":[{"name":"Shanxi Key Laboratory of Coal-Based Emerging Pollutant Identification and Risk Control, Research Center of Environment and Health, College of Environment and Resource, Shanxi University, Taiyuan 030006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanxin","family":"Ma","sequence":"additional","affiliation":[{"name":"Shanxi Key Laboratory of Coal-Based Emerging Pollutant Identification and Risk Control, Research Center of Environment and Health, College of Environment and Resource, Shanxi University, Taiyuan 030006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanxi Key Laboratory of Coal-Based Emerging Pollutant Identification and Risk Control, Research Center of Environment and Health, College of Environment and Resource, Shanxi University, Taiyuan 030006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifan","family":"Fan","sequence":"additional","affiliation":[{"name":"Shanxi Key Laboratory of Coal-Based Emerging Pollutant Identification and Risk Control, Research Center of Environment and Health, College of Environment and Resource, Shanxi University, Taiyuan 030006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Chen","sequence":"additional","affiliation":[{"name":"Shanxi Key Laboratory of Coal-Based Emerging Pollutant Identification and Risk Control, Research Center of Environment and Health, College of Environment and Resource, Shanxi University, Taiyuan 030006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiqi","family":"Yan","sequence":"additional","affiliation":[{"name":"Shanxi Key Laboratory of Coal-Based Emerging Pollutant Identification and Risk Control, Research Center of Environment and Health, College of Environment and Resource, Shanxi University, Taiyuan 030006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihua","family":"Ren","sequence":"additional","affiliation":[{"name":"Shanxi Key Laboratory of Coal-Based Emerging Pollutant Identification and Risk Control, Research Center of Environment and Health, College of Environment and Resource, Shanxi University, Taiyuan 030006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Ning","sequence":"additional","affiliation":[{"name":"Shanxi Key Laboratory of Coal-Based Emerging Pollutant Identification and Risk Control, Research Center of Environment and Health, College of Environment and Resource, Shanxi University, Taiyuan 030006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuting","family":"Wei","sequence":"additional","affiliation":[{"name":"First Hospital\/First Clinical Medical College, Shanxi Medical University, Taiyuan 030001, China"},{"name":"NHC Key Laboratory of Pneumoconiosis, Taiyuan 030001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9478-0201","authenticated-orcid":false,"given":"Tingting","family":"Ku","sequence":"additional","affiliation":[{"name":"Shanxi Key Laboratory of Coal-Based Emerging Pollutant Identification and Risk Control, Research Center of Environment and Health, College of Environment and Resource, Shanxi University, Taiyuan 030006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Niu, H., Xu, M., Tu, P., Xu, Y., Li, X., Xing, M., Chen, Z., Wang, X., Lou, X., and Wu, L. 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