Internalized polystyrene nanoplastics trigger testicular damage and promote ferroptosis via CISD1 downregulation in mouse spermatocyte
Abstract Background There is a growing body of research regarding the potential reproductive toxicity of microplastics and nanoplastics. However, the underlying mechanisms by which nanoplastics exposure adversely affects the testes remain poorly understood. Our study aims to clarify the relationship...
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BMC
2025-07-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03620-7 |
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| author | Jing Lv Guangyu Liu Ziqi Wang Jueshun Zhang Yuanyou Li Yifan Wang Ning Liu Shayakhmetova Altyn Zhongliang Jiang |
| author_facet | Jing Lv Guangyu Liu Ziqi Wang Jueshun Zhang Yuanyou Li Yifan Wang Ning Liu Shayakhmetova Altyn Zhongliang Jiang |
| author_sort | Jing Lv |
| collection | DOAJ |
| description | Abstract Background There is a growing body of research regarding the potential reproductive toxicity of microplastics and nanoplastics. However, the underlying mechanisms by which nanoplastics exposure adversely affects the testes remain poorly understood. Our study aims to clarify the relationship between ferritinophagy and mitochondrial dysfunction based on polystyrene nanoplastics (PS-NPs)-caused testicular damage in mice. Results The current study demonstrates that 50 nm PS-NPs accumulate in mouse testes and lead to a decrease in sperm quality and disruption of spermatocyte. Furthermore, PS-NPs trigger ferroptosis in GC-2 cells, which can be mitigated by deferiprone and 3-methyladenine. Further investigation reveals that PS-NPs initially aggregate in lysosomes and subsequently transfer to the mitochondria. This process increases mitochondrial Fe2+ and mitochondrial ROS levels, as well as reduces the expression of CISD1, a protein that inhibits the uptake and transport of Fe2+ into the mitochondrial matrix. These changes ultimately result in disturbances to mitochondrial structure and function. In terms of mechanism, pioglitazone, a drug that stabilizes CISD1, has been demonstrated to mitigate ferroptosis induced by NCOA4-mediated ferritinophagy in GC-2 cells. Conclusions Our results indicate that PS-NPs cause mouse testicular damage through ferroptosis. Mechanistically, we confirmed that PS-NPs trigger NCOA4-mediated ferritinophagy and CISD1 downregulation in spermatocyte, which aggravates the flow of ferrous iron from the cytoplasm to the mitochondria. |
| format | Article |
| id | doaj-art-3819cd08dc1f4e088eb305347a782f3e |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-3819cd08dc1f4e088eb305347a782f3e2025-08-20T04:02:55ZengBMCJournal of Nanobiotechnology1477-31552025-07-0123112010.1186/s12951-025-03620-7Internalized polystyrene nanoplastics trigger testicular damage and promote ferroptosis via CISD1 downregulation in mouse spermatocyteJing Lv0Guangyu Liu1Ziqi Wang2Jueshun Zhang3Yuanyou Li4Yifan Wang5Ning Liu6Shayakhmetova Altyn7Zhongliang Jiang8Key Laboratory of Animal Genetic, Breeding and Reproduction in Shaanxi Province, College of Animal Science and Technology, Northwest A&F UniversityKey Laboratory of Animal Genetic, Breeding and Reproduction in Shaanxi Province, College of Animal Science and Technology, Northwest A&F UniversityKey Laboratory of Animal Genetic, Breeding and Reproduction in Shaanxi Province, College of Animal Science and Technology, Northwest A&F UniversityKey Laboratory of Animal Genetic, Breeding and Reproduction in Shaanxi Province, College of Animal Science and Technology, Northwest A&F UniversityKey Laboratory of Bio-Resources and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan UniversityKey Laboratory of Animal Genetic, Breeding and Reproduction in Shaanxi Province, College of Animal Science and Technology, Northwest A&F UniversityKey Laboratory of Animal Genetic, Breeding and Reproduction in Shaanxi Province, College of Animal Science and Technology, Northwest A&F UniversityAgrotechnological Faculty, M.Kozybayev North Kazakhstan UniversityKey Laboratory of Animal Genetic, Breeding and Reproduction in Shaanxi Province, College of Animal Science and Technology, Northwest A&F UniversityAbstract Background There is a growing body of research regarding the potential reproductive toxicity of microplastics and nanoplastics. However, the underlying mechanisms by which nanoplastics exposure adversely affects the testes remain poorly understood. Our study aims to clarify the relationship between ferritinophagy and mitochondrial dysfunction based on polystyrene nanoplastics (PS-NPs)-caused testicular damage in mice. Results The current study demonstrates that 50 nm PS-NPs accumulate in mouse testes and lead to a decrease in sperm quality and disruption of spermatocyte. Furthermore, PS-NPs trigger ferroptosis in GC-2 cells, which can be mitigated by deferiprone and 3-methyladenine. Further investigation reveals that PS-NPs initially aggregate in lysosomes and subsequently transfer to the mitochondria. This process increases mitochondrial Fe2+ and mitochondrial ROS levels, as well as reduces the expression of CISD1, a protein that inhibits the uptake and transport of Fe2+ into the mitochondrial matrix. These changes ultimately result in disturbances to mitochondrial structure and function. In terms of mechanism, pioglitazone, a drug that stabilizes CISD1, has been demonstrated to mitigate ferroptosis induced by NCOA4-mediated ferritinophagy in GC-2 cells. Conclusions Our results indicate that PS-NPs cause mouse testicular damage through ferroptosis. Mechanistically, we confirmed that PS-NPs trigger NCOA4-mediated ferritinophagy and CISD1 downregulation in spermatocyte, which aggravates the flow of ferrous iron from the cytoplasm to the mitochondria.https://doi.org/10.1186/s12951-025-03620-7Polystyrene nanoplasticsTestesSpermatocyteFerritinophagyCISD1 |
| spellingShingle | Jing Lv Guangyu Liu Ziqi Wang Jueshun Zhang Yuanyou Li Yifan Wang Ning Liu Shayakhmetova Altyn Zhongliang Jiang Internalized polystyrene nanoplastics trigger testicular damage and promote ferroptosis via CISD1 downregulation in mouse spermatocyte Journal of Nanobiotechnology Polystyrene nanoplastics Testes Spermatocyte Ferritinophagy CISD1 |
| title | Internalized polystyrene nanoplastics trigger testicular damage and promote ferroptosis via CISD1 downregulation in mouse spermatocyte |
| title_full | Internalized polystyrene nanoplastics trigger testicular damage and promote ferroptosis via CISD1 downregulation in mouse spermatocyte |
| title_fullStr | Internalized polystyrene nanoplastics trigger testicular damage and promote ferroptosis via CISD1 downregulation in mouse spermatocyte |
| title_full_unstemmed | Internalized polystyrene nanoplastics trigger testicular damage and promote ferroptosis via CISD1 downregulation in mouse spermatocyte |
| title_short | Internalized polystyrene nanoplastics trigger testicular damage and promote ferroptosis via CISD1 downregulation in mouse spermatocyte |
| title_sort | internalized polystyrene nanoplastics trigger testicular damage and promote ferroptosis via cisd1 downregulation in mouse spermatocyte |
| topic | Polystyrene nanoplastics Testes Spermatocyte Ferritinophagy CISD1 |
| url | https://doi.org/10.1186/s12951-025-03620-7 |
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