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Therefore, assessing the male reproductive toxicity of anti\u2010cancer drug treatments and the potential for recovery is of paramount importance. However, in vivo evaluations are time\u2010intensive and require large numbers of animals. To overcome these constraints, we utilized an innovative organ culture system that supports long\u2010term spermatogenesis by placing the testis tissue between a base agarose gel and a polydimethylsiloxane ceiling, effectively mirroring the in vivo testicular environment. The present study aimed to determine the efficacy of this organ culture system for accurately assessing testicular toxicity induced by cisplatin, using acrosin\u2010green fluorescent protein (GFP) transgenic neonatal mouse testes. The testis fragments were treated with different concentrations of cisplatin\u2010containing medium for 24\u2009h and incubated in fresh medium for up to 70\u2009days. The changes in tissue volume and GFP fluorescence over time were evaluated to monitor the progression of spermatogenesis, in addition to the corresponding histopathology. Cisplatin treatment caused tissue volume shrinkage and reduced GFP fluorescence in a concentration\u2010dependent manner. Recovery from testicular toxicity was also dependent on the concentration of cisplatin received. The results demonstrated that this novel in vitro system can be a faithful replacement for animal experiments to assess the testicular toxicity of anti\u2010cancer drugs and their reversibility, providing a useful method for drug development.<\/jats:p>","DOI":"10.1002\/jat.4584","type":"journal-article","created":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T19:45:42Z","timestamp":1706039142000},"page":"784-793","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A novel alternative method for long\u2010term evaluation of male reproductive toxicity and its recovery using a pre\u2010pubertal mouse testis organ culture system"],"prefix":"10.1002","volume":"44","author":[{"given":"Kiyoshi","family":"Hashimoto","sequence":"first","affiliation":[{"name":"Department of Urology, Graduate School of Medicine Yokohama City University  Yokohama Kanagawa Japan"},{"name":"Department of Regenerative Medicine, Graduate School of Medicine Yokohama City University  Yokohama Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Arakawa","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences Kanazawa University  Kanazawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rikako","family":"Imamura","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences Kanazawa University  Kanazawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takuya","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Division of Cellular and Molecular Toxicology, Center for Biological Safety and Research National Institute of Health Sciences  Kawasaki Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Kitajima","sequence":"additional","affiliation":[{"name":"Division of Cellular and Molecular Toxicology, Center for Biological Safety and Research National Institute of Health Sciences  Kawasaki Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takuya","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine, Graduate School of Medicine Yokohama City University  Yokohama Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuhide","family":"Makiyama","sequence":"additional","affiliation":[{"name":"Department of Urology, Graduate School of Medicine Yokohama City University  Yokohama Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takehiko","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine, Graduate School of Medicine Yokohama City University  Yokohama Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7660-6303","authenticated-orcid":false,"given":"Satoshi","family":"Yokota","sequence":"additional","affiliation":[{"name":"Division of Cellular and Molecular Toxicology, Center for Biological Safety and Research National Institute of Health Sciences  Kawasaki Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,1,23]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/aja.2011.112"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.b21-00875"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1039\/c8lc00796a"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdrb.21188"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/jat\/28.2.138"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD008792.pub2"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.1989.7.1.100"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac980656z"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002280100319"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0283773"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod28.5.1217"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2014.03.019"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-39323-y"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-022-03449-y"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/jjco\/28.3.168"},{"key":"e_1_2_9_17_1","unstructured":"International Conference on Harmonization [ICH] Harmonised Guideline. 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