Internalized polystyrene nanoplastics trigger testicular damage and promote ferroptosis via CISD1 downregulation in mouse spermatocyte
Lv J. Liu G. Wang Z. Zhang J. Li Y. Wang Y. Liu N. Altyn S. Jiang Z.
December 2025BioMed Central Ltd
Journal of Nanobiotechnology
2025#23Issue 1
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.
CISD1 , Ferritinophagy , Polystyrene nanoplastics , Spermatocyte , Testes
Text of the article Перейти на текст статьи
Key Laboratory of Animal Genetic, Breeding and Reproduction in Shaanxi Province, College of Animal Science and Technology, Northwest A & F University, Shaanxi 712100, Yangling, China
Key Laboratory of Bio-Resources and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, 610065, China
Agrotechnological Faculty, M.Kozybayev North Kazakhstan University, Petropavlovsk, 150000, Kazakhstan
Key Laboratory of Animal Genetic
Key Laboratory of Bio-Resources and Eco-Environment of Ministry of Education
Agrotechnological Faculty
10 лет помогаем публиковать статьи Международный издатель
Книга Публикация научной статьи Волощук 2026 Book Publication of a scientific article 2026