{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T10:44:57Z","timestamp":1791801897552,"version":"4.3.4"},"reference-count":81,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":77,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Reprod Medicine &amp; Biology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Male infertility due to spermatogenic failure remains a global challenge. While in\u00a0vitro spermatogenesis (IVS) offers potential for fertility preservation, recapitulating the complex, species\u2010specific testicular niche remains a formidable task. This review evaluates IVS progress and bottlenecks across rodents, primates, domestic animals, and humans.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This review summarizes a comprehensive literature synthesis of IVS methodologies, including organ culture, microfluidics, 3D organoids, and induced pluripotent stem cell (iPSC)\u2010derived systems. Particular focus was placed on the technical evolution from the foundational gas\u2013liquid interface method to the development of bioengineering platforms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main Findings<\/jats:title>\n                    <jats:p>Murine IVS systems have successfully and consistently produced fertile offspring. Conversely, human and non\u2010human primate models show meiotic arrest, with differentiation typically stagnating at pre\u2010meiotic stages. Although domestic animal models have occasionally yielded haploid cells, efficiency remains low. Recent single\u2010cell analyses suggest that disrupted somatic\u2010germ cell communication is a key driver of these failures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Bridging the gap between rodent success and human application requires integrating developmental biology with precision engineering. Future efforts must focus on establishing rigorous epigenetic and functional validation to ensure the safety and efficacy of IVS for clinical reproductive medicine.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/rmb2.70044","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T04:48:03Z","timestamp":1773982083000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Advancements in Spermatogenesis In\u00a0Vitro: From Murine Success to Human Applications"],"prefix":"10.1002","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7853-5164","authenticated-orcid":false,"given":"Maki","family":"Kamoshita","sequence":"first","affiliation":[{"name":"Graduate School of Veterinary Science Azabu University  Sagamihara Japan"},{"name":"School of Veterinary Medicine Azabu University  Sagamihara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,19]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmx036"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2017.03.025"},{"issue":"5","key":"e_1_2_10_4_1","first-page":"277","article-title":"Mini Bioreactor Can Support In\u00a0Vitro Spermatogenesis of Mouse Testicular Tissue","volume":"24","author":"Amirkhani Z.","year":"2022","journal-title":"Cell Journal (Yakhteh)"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2016.11.012"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.56808\/2985-1130.3239"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10815-020-01912-5"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.110868"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/reprodmed4030020"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/ani12172283"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.theriogenology.2023.12.013"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/01485010390219656"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.22855"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.theriogenology.2016.12.002"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12327"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anireprosci.2009.06.018"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2012.07.015"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2024.1532107"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12015-024-10726-2"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.110.083899"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00013.2015"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2020.12.004"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-022-03449-y"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.104523"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.4103\/1008-682X.154994"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12182234"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/ani13010128"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2021.08.005"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.102.004986"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-84965-1"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.103.017012"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.102.008516"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-101512-122353"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI170140"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2022.884122"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xfss.2021.09.001"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.26822"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-15799-3"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep21472"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/rmb2.12225"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0407063101"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2005.12.028"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/ani12213026"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-39304-1"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-82792-2"},{"issue":"1","key":"e_1_2_10_46_1","first-page":"32","article-title":"Preserved Seminiferous Tubule Integrity With Spermatogonial Survival and Induction of Sertoli and Leydig Cell Maturation After Long\u2010Term Organotypic Culture of Prepubertal Human Testicular Tissue","volume":"32","author":"Michele F.","year":"2017","journal-title":"Human Reproduction"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07526-6"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.3389\/fvets.2022.894075"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2024.101320"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/aor.14643"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-63805-4"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1262\/jrd.2023-093"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ggedit.2022.100014"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.204683"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-024-01258-3"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cryobiol.2021.02.006"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2023.108391"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deac245"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12015-021-10198-8"},{"issue":"2","key":"e_1_2_10_60_1","first-page":"93","article-title":"Isolation and Proliferation of Spermatogonial Cells From Ghezel Sheep","volume":"10","author":"Qasemi\u2010Panahi B.","year":"2018","journal-title":"Avicenna Journal of Medical Biotechnology"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1088\/1758-5090\/ad618f"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.757565"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-021-02322-8"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1093\/biolre\/ioz053"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09850"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms1478"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.13325"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.82263"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4827(64)90156-9"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-74-5-788"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.89480"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2025.06.022"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0967199403002363"},{"key":"e_1_2_10_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4827(59)90201-0"},{"key":"e_1_2_10_75_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20215476"},{"key":"e_1_2_10_76_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.70152"},{"key":"e_1_2_10_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2018.04.180"},{"key":"e_1_2_10_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virs.2022.10.001"},{"key":"e_1_2_10_79_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.113.108613"},{"key":"e_1_2_10_80_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-62703-038-0_41"},{"key":"e_1_2_10_81_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gaz043"},{"key":"e_1_2_10_82_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.17197"}],"container-title":["Reproductive Medicine and Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/rmb2.70044","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/rmb2.70044","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/rmb2.70044","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T09:49:05Z","timestamp":1791798545000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/rmb2.70044"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":81,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1002\/rmb2.70044"],"URL":"https:\/\/doi.org\/10.1002\/rmb2.70044","archive":["Portico"],"relation":{},"ISSN":["1445-5781","1447-0578"],"issn-type":[{"value":"1445-5781","type":"print"},{"value":"1447-0578","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2026-02-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70044"}}