{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T16:31:51Z","timestamp":1786638711270,"version":"build-2736575974"},"reference-count":86,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,8,12]],"date-time":"2018-08-12T00:00:00Z","timestamp":1534032000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008672","name":"Yamaguchi Endocrine Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008672","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Reprod Medicine &amp; Biology"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Spermatogenesis is one of the most complicated cellular differentiation processes in a body. Researchers struggled to find and develop a micro\u2010environmental condition that can support the process in vitro. Such endeavors can be traced back to a century ago and are yet continuing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Reports on in vitro spermatogenesis and related works were selected and classified into four categories based on the method used; organ culture, tubule culture, cell culture, and 3\u2010dimensional cell culture methods. Each report was critically reviewed from the present point of view by authors who have been working on in vitro spermatogenesis with organ culture method over a decade.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The organ culture method has the longest history and is the most successful method, which produced fertile mouse sperm from spermatogonial stem cells. Formulation of the medium was a key factor, most importantly serum\u2010derived substances. However, factors in the serum that induce and support spermatogenesis in the cultured tissue remain to be identified. In addition, the success of mouse spermatogenesis is yet to be applied to other animals. On looking into the history of cell culture method, it became clear that Sertoli cells as feeder cells play an important role. Even with Sertoli cells, however, spermatogenic development has been limited to small parts of spermatogenesis, a segmented period of meiotic prophase for instance. Recent developments of organoid or 3\u2010dimensional culture techniques are promising but they still need further refinements.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The study of in vitro spermatogenesis progressed significantly over the last century. We need more work, however, to establish a culture system that can induce and maintain complete spermatogenesis of many if not all mammalian species.<\/jats:p><\/jats:sec>","DOI":"10.1002\/rmb2.12225","type":"journal-article","created":{"date-parts":[[2018,8,13]],"date-time":"2018-08-13T00:59:39Z","timestamp":1534121979000},"page":"407-420","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["In vitro spermatogenesis: A century\u2010long research journey, still half way around"],"prefix":"10.1002","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0744-7492","authenticated-orcid":false,"given":"Mitsuru","family":"Komeya","sequence":"first","affiliation":[{"name":"Department of Urology Yokohama City University Graduate School of Medicine Yokohama Kanagawa Japan"},{"name":"Laboratory of Biopharmaceutical and Regenerative Sciences Institute of Molecular Medicine and Life Science Yokohama City University Association of Medical Science Yokohama Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Sato","sequence":"additional","affiliation":[{"name":"Laboratory of Biopharmaceutical and Regenerative Sciences Institute of Molecular Medicine and Life Science Yokohama City University Association of Medical Science Yokohama Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1422-0317","authenticated-orcid":false,"given":"Takehiko","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Department of Urology Yokohama City University Graduate School of Medicine Yokohama Kanagawa Japan"},{"name":"Laboratory of Biopharmaceutical and Regenerative Sciences Institute of Molecular Medicine and Life Science Yokohama City University Association of Medical Science Yokohama Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,8,12]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.2164\/jandrol.107.004655"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/aja.1000990307"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.1090310208"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1530\/REP-17-0391"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1530\/REP-16-0588"},{"key":"e_1_2_10_7_1","first-page":"461","article-title":"De la m\u00e9thode de culture des tissus. VI. Le testicule","volume":"60","author":"Champy CH","year":"1920","journal-title":"Arch Zool Exptl Gen"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.1938.0024"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4827(59)90201-0"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/rmb2.12024"},{"key":"e_1_2_10_11_1","first-page":"372","article-title":"Growth of rat testes fragments in organ culture","volume":"22","author":"Steinberger A","year":"1963","journal-title":"Fed Proc"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.1091480409"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-74-5-788"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4827(64)90156-9"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1530\/jrf.0.0090243"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4827(66)90449-6"},{"issue":"2","key":"e_1_2_10_17_1","first-page":"117","article-title":"Factors affecting spermatogenesis in organ cultures of mammalian testes","author":"Steinberger A","year":"1967","journal-title":"J Reprod Fertil"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02618371"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1530\/jrf.0.0560099"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.0940043"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-114-3-801"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod28.5.1217"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2605.1995.tb00928.x"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.115.135145"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod48.4.761"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0967199403002363"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1508\/cytologia.36.298"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-5223.1974.tb01448.x"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00295480"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.108.067926"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2014.160"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.110.083899"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09850"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0192884"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.103.017012"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1679\/aohc.67.297"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0407063101"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms1478"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1211845109"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5320"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0130171"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.theriogenology.2015.09.012"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0116660"},{"key":"e_1_2_10_44_1","first-page":"819","article-title":"Vitamin A prevents round spermatid nuclear damage and promotes the production of motile sperm during in vitro maturation of vitrified pre\u2010pubertal mouse testicular tissue","volume":"22","author":"Dumont L","year":"2016","journal-title":"Mol Hum Reprod"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12958-017-0305-y"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdr2.1002"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1442-2042.2012.02979.x"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep21472"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-15799-3"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.1091850307"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.1091740404"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/0303-7207(76)90082-4"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-112-3-1150"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1939-4640.1985.tb03289.x"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1177\/34.8.3734416"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4827(66)90451-4"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1439-0272.1983.tb00368.x"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.80.11.3377"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02621259"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(91)91935-6"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90543-Y"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4827(92)90291-F"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.12.5533"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1073162"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod59.2.379"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1006\/excr.2000.4998"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1677\/jme.1.01493"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.102.015099"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10815-010-9442-3"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/13.10.2772"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/15.8.1713"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/14.5.1287"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod42.2.301"},{"key":"e_1_2_10_74_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/17.1.161"},{"key":"e_1_2_10_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(02)04833-1"},{"key":"e_1_2_10_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2012.05.039"},{"key":"e_1_2_10_77_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.102.004986"},{"key":"e_1_2_10_78_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1439-0531.2008.01281.x"},{"key":"e_1_2_10_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2005.12.028"},{"key":"e_1_2_10_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2006.09.015"},{"key":"e_1_2_10_81_1","doi-asserted-by":"publisher","DOI":"10.2164\/jandrol.107.002857"},{"key":"e_1_2_10_82_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gap052"},{"key":"e_1_2_10_83_1","doi-asserted-by":"publisher","DOI":"10.1038\/aja.2011.112"},{"key":"e_1_2_10_84_1","doi-asserted-by":"publisher","DOI":"10.4103\/1008-682X.154994"},{"key":"e_1_2_10_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2010.02.029"},{"key":"e_1_2_10_86_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.106.056895"},{"key":"e_1_2_10_87_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.113.108613"}],"container-title":["Reproductive Medicine and Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Frmb2.12225","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/rmb2.12225","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,17]],"date-time":"2023-09-17T05:50:53Z","timestamp":1694929853000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/rmb2.12225"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,12]]},"references-count":86,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2018,10]]}},"alternative-id":["10.1002\/rmb2.12225"],"URL":"https:\/\/doi.org\/10.1002\/rmb2.12225","archive":["Portico"],"relation":{},"ISSN":["1445-5781","1447-0578"],"issn-type":[{"value":"1445-5781","type":"print"},{"value":"1447-0578","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,8,12]]},"assertion":[{"value":"2018-06-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-07-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}