Baicalin targets YTHDC2 and alleviates male reproductive toxicity caused by co-exposure to nanoplastics and manganese through m6A-dependent pathway
Abstract Nanoplastics (NPs) pollution has become a pressing global environmental issue. NPs possess the ability to adsorb heavy metals, thereby acting as vectors that facilitate the entry of these toxic substances into living organisms. However, the synergistic toxic effects of NPs and heavy metals,...
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BMC
2025-06-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03535-3 |
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| author | Yi Wen Tingwei Pan Lu Liu Jinning Wang Kexin Yang Zhushan Fu Wenhao Li XinMiao Wang Zhiru Shen Yan Li Yinke Du Yu Deng |
| author_facet | Yi Wen Tingwei Pan Lu Liu Jinning Wang Kexin Yang Zhushan Fu Wenhao Li XinMiao Wang Zhiru Shen Yan Li Yinke Du Yu Deng |
| author_sort | Yi Wen |
| collection | DOAJ |
| description | Abstract Nanoplastics (NPs) pollution has become a pressing global environmental issue. NPs possess the ability to adsorb heavy metals, thereby acting as vectors that facilitate the entry of these toxic substances into living organisms. However, the synergistic toxic effects of NPs and heavy metals, particularly with regard to male reproductive health, remain poorly understood. This study establishes in vivo and in vitro models to assess the effects of single and co-exposure to polystyrene nanoplastics (PS-NPs, 0.1 μm) and manganese (Mn) on male reproductive function. Our results reveal that co-exposure leads to a synergistic toxic effect, aggravating testicular damage, sperm abnormalities, and hormone disruption. Mechanistically, PS-NPs and Mn collaboratively suppress the RNA-binding protein YTHDC2, which in turn impairs Mdm2 transcription and translation in an m6A-dependent manner. This disruption results in cell cycle arrest via the Mdm2-p53 pathway, ultimately hindering spermatogenesis. Notably, baicalin, a natural compound, effectively targets YTHDC2 and mitigates the reproductive toxicity induced by co-exposure. These findings provide the novel evidence of the synergistic reproductive toxicity of PS-NPs and Mn in male mammals, offering new insights into their combined toxic effects and highlighting the potential of baicalin as a therapeutic intervention. Graphical Abstract |
| format | Article |
| id | doaj-art-a8c57e2eaaa041229462ef0b328c4ee6 |
| institution | OA Journals |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-a8c57e2eaaa041229462ef0b328c4ee62025-08-20T02:10:31ZengBMCJournal of Nanobiotechnology1477-31552025-06-0123112110.1186/s12951-025-03535-3Baicalin targets YTHDC2 and alleviates male reproductive toxicity caused by co-exposure to nanoplastics and manganese through m6A-dependent pathwayYi Wen0Tingwei Pan1Lu Liu2Jinning Wang3Kexin Yang4Zhushan Fu5Wenhao Li6XinMiao Wang7Zhiru Shen8Yan Li9Yinke Du10Yu Deng11Department of Environmental Health, School of Public Health, China Medical UniversityDepartment of Environmental Health, School of Public Health, China Medical UniversityDepartment of Environmental Health, School of Public Health, China Medical UniversityDepartment of Environmental Health, School of Public Health, China Medical UniversityDepartment of Environmental Health, School of Public Health, China Medical UniversityDepartment of Environmental Health, School of Public Health, China Medical UniversityDepartment of Environmental Health, School of Public Health, China Medical UniversityDepartment of Environmental Health, School of Public Health, China Medical UniversityDepartment of Environmental Health, School of Public Health, China Medical UniversitySchool of Medical Information Engineering, Zunyi Medical UniversityDepartment of Nephrology, The First Hospital of China Medical UniversityDepartment of Environmental Health, School of Public Health, China Medical UniversityAbstract Nanoplastics (NPs) pollution has become a pressing global environmental issue. NPs possess the ability to adsorb heavy metals, thereby acting as vectors that facilitate the entry of these toxic substances into living organisms. However, the synergistic toxic effects of NPs and heavy metals, particularly with regard to male reproductive health, remain poorly understood. This study establishes in vivo and in vitro models to assess the effects of single and co-exposure to polystyrene nanoplastics (PS-NPs, 0.1 μm) and manganese (Mn) on male reproductive function. Our results reveal that co-exposure leads to a synergistic toxic effect, aggravating testicular damage, sperm abnormalities, and hormone disruption. Mechanistically, PS-NPs and Mn collaboratively suppress the RNA-binding protein YTHDC2, which in turn impairs Mdm2 transcription and translation in an m6A-dependent manner. This disruption results in cell cycle arrest via the Mdm2-p53 pathway, ultimately hindering spermatogenesis. Notably, baicalin, a natural compound, effectively targets YTHDC2 and mitigates the reproductive toxicity induced by co-exposure. These findings provide the novel evidence of the synergistic reproductive toxicity of PS-NPs and Mn in male mammals, offering new insights into their combined toxic effects and highlighting the potential of baicalin as a therapeutic intervention. Graphical Abstracthttps://doi.org/10.1186/s12951-025-03535-3Polystyrene nanoplasticsManganeseMale reproductive toxicitym6AMdm2-p53 PathwayBaicalin |
| spellingShingle | Yi Wen Tingwei Pan Lu Liu Jinning Wang Kexin Yang Zhushan Fu Wenhao Li XinMiao Wang Zhiru Shen Yan Li Yinke Du Yu Deng Baicalin targets YTHDC2 and alleviates male reproductive toxicity caused by co-exposure to nanoplastics and manganese through m6A-dependent pathway Journal of Nanobiotechnology Polystyrene nanoplastics Manganese Male reproductive toxicity m6A Mdm2-p53 Pathway Baicalin |
| title | Baicalin targets YTHDC2 and alleviates male reproductive toxicity caused by co-exposure to nanoplastics and manganese through m6A-dependent pathway |
| title_full | Baicalin targets YTHDC2 and alleviates male reproductive toxicity caused by co-exposure to nanoplastics and manganese through m6A-dependent pathway |
| title_fullStr | Baicalin targets YTHDC2 and alleviates male reproductive toxicity caused by co-exposure to nanoplastics and manganese through m6A-dependent pathway |
| title_full_unstemmed | Baicalin targets YTHDC2 and alleviates male reproductive toxicity caused by co-exposure to nanoplastics and manganese through m6A-dependent pathway |
| title_short | Baicalin targets YTHDC2 and alleviates male reproductive toxicity caused by co-exposure to nanoplastics and manganese through m6A-dependent pathway |
| title_sort | baicalin targets ythdc2 and alleviates male reproductive toxicity caused by co exposure to nanoplastics and manganese through m6a dependent pathway |
| topic | Polystyrene nanoplastics Manganese Male reproductive toxicity m6A Mdm2-p53 Pathway Baicalin |
| url | https://doi.org/10.1186/s12951-025-03535-3 |
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