{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:59:00Z","timestamp":1787029140292,"version":"build-2736575974"},"reference-count":38,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T00:00:00Z","timestamp":1713312000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["81502783"],"award-info":[{"award-number":["81502783"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nanomaterials"],"abstract":"<jats:p>Reproductive disorders and declining fertility rates are significant public health concerns affecting birth rates and future populations. Male infertility, often due to spermatogenesis defects, may be linked to environmental pollutants like nickel nanoparticles (Ni NPs). Ni NPs are extensively utilized across different industries. Nevertheless, their potential adverse effects cannot be overlooked. Previous studies have linked the reproductive toxicity induced by Ni NPs with disturbances in mitochondrial function. Mitochondrial division\/fusion dynamics are crucial to their proper function, yet little is known about how Ni NPs perturb these dynamics and whether such perturbation contributes to the impairment of the male reproductive system. Herein, we demonstrated that the exposure of Ni NPs to the mouse-derived spermatogonia cell line (GC-1 cells) triggered DRP1-mediated mitochondrial division and the enhanced impairment of mitochondria, consequently promoting mitochondria-dependent cell apoptosis. Notably, both the mitochondrial division inhibitor (Mdivi-1) and lentiviral-transfected cells with low expression of Dnm1l-DK in these cells could mitigate the toxic effects induced by Ni NPs, pointing to the potential role of mitochondrial dynamics in Ni NP-induced reproductive toxicity. Collectively, our work contributes to the understanding of the mechanisms by which Ni NPs can impact male reproductive function and identifies mitochondrial division as a potential target for intervention.<\/jats:p>","DOI":"10.3390\/nano14080689","type":"journal-article","created":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T09:15:20Z","timestamp":1713345320000},"page":"689","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Mitochondrial Fission in Nickel Nanoparticle-Induced Reproductive Toxicity: An In Vitro GC-1 Cell Study"],"prefix":"10.3390","volume":"14","author":[{"given":"Hanyue","family":"Zheng","sequence":"first","affiliation":[{"name":"Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geyu","family":"Liang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunliu","family":"Guan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahui","family":"Dong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6012-1611","authenticated-orcid":false,"given":"Jinshun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Allegheny Health Network Cancer Institute, Pittsburgh, PA 15212, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Tang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Kong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"70","DOI":"10.2307\/2953365","article-title":"Public knowledge and perceptions about unplanned pregnancy and contraception in three countries","volume":"29","author":"Delbanco","year":"1997","journal-title":"Fam. Plan. Perspect."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Ilacqua, A., Izzo, G., Emerenziani, G.P., Baldari, C., and Aversa, A. (2018). Lifestyle and fertility: The influence of stress and quality of life on male fertility. Reprod. Biol. Endocrinol., 16.","DOI":"10.1186\/s12958-018-0436-9"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"188","DOI":"10.4103\/iju.IJU_407_16","article-title":"Semen culture and the assessment of genitourinary tract infections","volume":"33","author":"Solomon","year":"2017","journal-title":"Indian J. Urol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1007\/s00105-018-4307-2","article-title":"Impact of lifestyle and environmental factors on male reproductive health","volume":"69","author":"Schuppe","year":"2018","journal-title":"Hautarzt"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1093\/toxsci\/kfz023","article-title":"Polycyclic Aromatic Hydrocarbons and Endocrine Disruption: Role of Testicular Gap Junctional Intercellular Communication and Connexins","volume":"169","author":"Kubincova","year":"2019","journal-title":"Toxicol. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1093\/toxsci\/kfr206","article-title":"Bioavailability, intracellular mobilization of nickel, and HIF-1\u03b1 activation in human lung epithelial cells exposed to metallic nickel and nickel oxide nanoparticles","volume":"124","author":"Pietruska","year":"2011","journal-title":"Toxicol. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Mo, Y., Jiang, M., Zhang, Y., Wan, R., Li, J., Zhong, C.-J., Li, H., Tang, S., and Zhang, Q. (2019). Comparative mouse lung injury by nickel nanoparticles with differential surface modification. J. Nanobiotechnol., 17.","DOI":"10.1186\/s12951-018-0436-0"},{"key":"ref_8","first-page":"1393","article-title":"Acute toxicity of nickel nanoparticles in rats after intravenous injection","volume":"9","author":"Magaye","year":"2014","journal-title":"Int. J. Nanomed."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1080\/17435390.2020.1808727","article-title":"miR-21 mediates nickel nanoparticle-induced pulmonary injury and fibrosis","volume":"14","author":"Mo","year":"2020","journal-title":"Nanotoxicology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"21253","DOI":"10.3390\/ijms151121253","article-title":"Nickel Nanoparticles Exposure and Reproductive Toxicity in Healthy Adult Rats","volume":"15","author":"Kong","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000362163","article-title":"Embryonic toxicity of nanoparticles","volume":"199","author":"Petra","year":"2014","journal-title":"Cells Tissues Organs"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3389\/fnmol.2018.00003","article-title":"Mitochondrial Division Inhibitor 1 (mdivi-1) Protects Neurons against Excitotoxicity through the Modulation of Mitochondrial Function and Intracellular Ca2+ Signaling","volume":"11","author":"Asier","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"C461","DOI":"10.1152\/ajpcell.00388.2021","article-title":"The importance of mitochondrial quality control for maintaining skeletal muscle function across health span","volume":"322","author":"Sligar","year":"2022","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/s41565-019-0373-6","article-title":"Carbon-dot-supported atomically dispersed gold as a mitochondrial oxidative stress amplifier for cancer treatment","volume":"14","author":"Gong","year":"2019","journal-title":"Nat. Nanotechnol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41565-021-01006-y","article-title":"Cancer cells hijack T-cell mitochondria","volume":"17","author":"Baldwin","year":"2022","journal-title":"Nat. Nanotechnol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/164_2016_38","article-title":"Mitochondrial Fission in Human Diseases","volume":"240","author":"Serasinghe","year":"2017","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1042\/EBC20170104","article-title":"Mitochondrial dynamics: Overview of molecular mechanisms","volume":"62","author":"Tilokani","year":"2018","journal-title":"Essays Biochem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1093\/jb\/mvz106","article-title":"Mitochondrial division, fusion and degradation","volume":"167","author":"Murata","year":"2020","journal-title":"J. Biochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"105449","DOI":"10.1016\/j.actatropica.2020.105449","article-title":"Lipoic acid alleviates schistosomiasis-induced liver fibrosis by upregulating Drp1 phosphorylation","volume":"206","author":"Luo","year":"2020","journal-title":"Acta Trop."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.chemosphere.2018.11.128","article-title":"Mechanisms underlying nickel nanoparticle induced reproductive toxicity and chemo-protective effects of vitamin C in male rats","volume":"218","author":"Kong","year":"2019","journal-title":"Chemosphere"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.scitotenv.2019.07.107","article-title":"Molecular mechanisms underlying nickel nanoparticle induced rat Sertoli-germ cells apoptosis","volume":"692","author":"Kong","year":"2019","journal-title":"Sci. Total Environ."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Ruonan, W., Yuxiang, H., Lu, Y., Siyu, L., Jiayi, L., Biqi, H., Xiaoyan, Z., and Zhigang, Z. (2023). The role of mitochondrial dynamics imbalance in hexavalent chromium-induced apoptosis and autophagy in rat testis. Chem.-Biol. Interact., 374.","DOI":"10.1016\/j.cbi.2023.110424"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.tox.2017.07.019","article-title":"Mitochondrial fusion, fission, and mitochondrial toxicity","volume":"391","author":"Meyer","year":"2017","journal-title":"Toxicology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e158447","DOI":"10.1172\/JCI158447","article-title":"Mitochondrial dysfunction in cell senescence and aging","volume":"132","author":"Miwa","year":"2022","journal-title":"J. Clin. Investig."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1002\/pro.4079","article-title":"Adenosine triphosphate energy-independently controls protein homeostasis with unique structure and diverse mechanisms","volume":"30","author":"Song","year":"2021","journal-title":"Protein Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e00211","DOI":"10.1002\/edm2.211","article-title":"The mechanism by which imeglimin inhibits gluconeogenesis in rat liver cells","volume":"4","author":"Vial","year":"2021","journal-title":"Endocrinol. Diabetes Metab."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"128346","DOI":"10.1016\/j.chemosphere.2020.128346","article-title":"Cadmium induced BEAS-2B cells apoptosis and mitochondria damage via MAPK signaling pathway","volume":"263","author":"Cao","year":"2021","journal-title":"Chemosphere"},{"key":"ref_28","unstructured":"Carpenter, R., and Brady, M.F. (2022). StatPearls, StatPearls Publishing LLC."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1111\/bjh.12757","article-title":"The role of apoptosis in megakaryocytes and platelets","volume":"165","author":"Kile","year":"2014","journal-title":"Br. J. Haematol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1177\/07482337211011008","article-title":"Toxicity assessment of metallic nickel nanoparticles in various biological models: An interplay of reactive oxygen species, oxidative stress, and apoptosis","volume":"37","author":"Iqbal","year":"2021","journal-title":"Toxicol. Ind. Health"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Thakur, M., Gupta, H., Singh, D., Mohanty, I.R., Maheswari, U., Vanage, G., and Joshi, D.S. (2014). Histopathological and ultra structural effects of nanoparticles on rat testis following 90 days (Chronic study) of repeated oral administration. J. Nanobiotechnol., 12.","DOI":"10.1186\/s12951-014-0042-8"},{"key":"ref_32","first-page":"392","article-title":"Impact of subchronic exposure to low-dose nano-nickel oxide on the reproductive function and offspring of male rats","volume":"25","author":"Fan","year":"2019","journal-title":"Zhonghua Nan Ke Xue Natl. J. Androl."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.chemosphere.2015.10.068","article-title":"Effects of nickel exposure on testicular function, oxidative stress, and male reproductive dysfunction in Spodoptera litura Fabricius","volume":"148","author":"Sun","year":"2016","journal-title":"Chemosphere"},{"key":"ref_34","unstructured":"Wu, Y. (2021). Study on Male Reproductive Toxicity of Nano-nickel and Preliminary Study on the Mechanism of Mitochondrial Division and Autophagy. [Master\u2019s Thesis, Southeast University]."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"8758","DOI":"10.1007\/s11356-019-04319-7","article-title":"Sulfur dioxide induces apoptosis via reactive oxygen species generation in rat cardiomyocytes","volume":"26","author":"Li","year":"2019","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e21620","DOI":"10.1096\/fj.202100067R","article-title":"Mitochondrial fusion and fission: The fine-tune balance for cellular homeostasis","volume":"35","author":"Adebayo","year":"2021","journal-title":"FASEB J."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Miao, J., Chen, W., Wang, P., Zhang, X., Wang, L., Wang, S., and Wang, Y. (2021). MFN1 and MFN2 Are Dispensable for Sperm Development and Functions in Mice. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222413507"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/j.stemcr.2020.03.024","article-title":"MFN2 Plays a Distinct Role from MFN1 in Regulating Spermatogonial Differentiation","volume":"14","author":"Chen","year":"2020","journal-title":"Stem Cell Rep."}],"container-title":["Nanomaterials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-4991\/14\/8\/689\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:29:02Z","timestamp":1760106542000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-4991\/14\/8\/689"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,17]]},"references-count":38,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["nano14080689"],"URL":"https:\/\/doi.org\/10.3390\/nano14080689","relation":{},"ISSN":["2079-4991"],"issn-type":[{"value":"2079-4991","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,17]]}}}