{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:08:48Z","timestamp":1792804128615,"version":"4.5.0"},"reference-count":43,"publisher":"IOP Publishing","issue":"1","license":[{"start":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T00:00:00Z","timestamp":1666828800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T00:00:00Z","timestamp":1666828800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/iopscience.iop.org\/info\/page\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"crossref","award":["2018A030313473"],"award-info":[{"award-number":["2018A030313473"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["31801235"],"award-info":[{"award-number":["31801235"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Guangzhou Science and Technology Program"},{"name":"Science and Technology Plan Project of Guangzhou","award":["201508020001"],"award-info":[{"award-number":["201508020001"]}]},{"name":"Special Innovation Projects of Universities"},{"name":"Key Project","award":["201803010044"],"award-info":[{"award-number":["201803010044"]}]},{"name":"Guangdong Province","award":["2019KTSCXo11"],"award-info":[{"award-number":["2019KTSCXo11"]}]}],"content-domain":{"domain":["iopscience.iop.org"],"crossmark-restriction":false},"short-container-title":["Biofabrication"],"published-print":{"date-parts":[[2023,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Increasing rates of male infertility require more experimental models to understand the mechanisms underlying male infertility. <jats:italic>In vitro<\/jats:italic> organoids hold unprecedented promise for this purpose; however, the development of organoids with tissue architecture similar to that of the testis <jats:italic>in vivo<\/jats:italic> remains a challenge. Here, we generated testicular organoids derived from testicular cells by combining a hanging drop culture and a rotation culture system. Our results indicated that testicular cells could self-assemble into spheroid organoids with tubule-like structures in hanging drop culture. The organoids can subsequently be cultured and maintained in a rotation culture system. These established organoids have gene expression profiles similar to those of adult testis tissue, produce testosterone with preserved gonadotropin responsiveness, and exhibit sensitivity to reproductive toxicants. More importantly, each testicular organoid can be generated from only 2000 cells, and they maintain their proliferative ability after freezing and thawing. These features make it possible to obtain fresh primary testis cells from testicular biopsies taken from patients or endangered wild species, and to build individual-specific biobanks. These findings will help enable the exploration of self-organization process of testicular cells and provide an experimental model for reproductive biology research, pharmacotoxicology testing, and regenerative medicine.<\/jats:p>","DOI":"10.1088\/1758-5090\/ac992a","type":"journal-article","created":{"date-parts":[[2022,10,11]],"date-time":"2022-10-11T22:18:41Z","timestamp":1665526721000},"page":"015001","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["In vitro reconstitution of the hormone-responsive testicular organoids from murine primary testicular cells"],"prefix":"10.1088","volume":"15","author":[{"given":"Yan","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rufei","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siying","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoyang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqing","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaling","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qihao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8879-3273","authenticated-orcid":true,"given":"Yadong","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"266","published-online":{"date-parts":[[2022,10,27]]},"reference":[{"key":"bfac992abib1","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1093\/humupd\/dmx021","article-title":"The diagnosis of male infertility: an analysis of the evidence to support the development of global WHO guidance-challenges and future research opportunities","volume":"23","author":"Barratt","year":"2017","journal-title":"Hum. Reprod. Update"},{"key":"bfac992abib2","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1093\/humupd\/dmv016","article-title":"Infertility around the globe: new thinking on gender, reproductive technologies and global movements in the 21st century","volume":"21","author":"Inhorn","year":"2015","journal-title":"Hum. Reprod. Update"},{"key":"bfac992abib3","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.tice.2013.12.001","article-title":"Reassembly of somatic cells and testicular organogenesis in vitro","volume":"46","author":"Reuter","year":"2014","journal-title":"Tissue Cell"},{"key":"bfac992abib4","doi-asserted-by":"publisher","first-page":"bqab033","DOI":"10.1210\/endocr\/bqab033","article-title":"Regulation of cell types within testicular organoids","volume":"162","author":"Lara","year":"2021","journal-title":"Endocrinology"},{"key":"bfac992abib5","doi-asserted-by":"publisher","first-page":"2139","DOI":"10.1242\/dev.107029","article-title":"Sertoli cells control peritubular myoid cell fate and support adult Leydig cell development in the prepubertal testis","volume":"141","author":"Rebourcet","year":"2014","journal-title":"Development"},{"key":"bfac992abib6","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1038\/s41422-020-0283-z","article-title":"In vitro testicular organogenesis from human fetal gonads produces fertilization-competent spermatids","volume":"30","author":"Yuan","year":"2020","journal-title":"Cell Res."},{"key":"bfac992abib7","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.1016\/j.drudis.2016.07.003","article-title":"Organoid-on-a-chip and body-on-a-chip systems for drug screening and disease modeling","volume":"21","author":"Skardal","year":"2016","journal-title":"Drug Discov. Today"},{"key":"bfac992abib8","doi-asserted-by":"publisher","first-page":"eaaf9414","DOI":"10.1126\/science.aaf9414","article-title":"Human tissues in a dish: the research and ethical implications of organoid technology","volume":"355","author":"Bredenoord","year":"2017","journal-title":"Science"},{"key":"bfac992abib9","doi-asserted-by":"publisher","first-page":"1586","DOI":"10.1016\/j.cell.2016.05.082","article-title":"Modeling development and disease with organoids","volume":"165","author":"Clevers","year":"2016","journal-title":"Cell"},{"key":"bfac992abib10","doi-asserted-by":"publisher","DOI":"10.1126\/science.1247125","article-title":"Organogenesis in a dish: modeling development and disease using organoid technologies","volume":"345","author":"Lancaster","year":"2014","journal-title":"Science"},{"key":"bfac992abib11","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/s41576-018-0051-9","article-title":"Progress and potential in organoid research","volume":"19","author":"Rossi","year":"2018","journal-title":"Nat. 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All that glitters is not gold!","volume":"25","author":"Mannello","year":"2007","journal-title":"Stem Cells"},{"key":"bfac992abib33","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1016\/j.fct.2017.05.001","article-title":"The use of KnockOut serum replacement (KSR) in three dimensional rat testicular cells co-culture model: an improved male reproductive toxicity testing system","volume":"106","author":"Zhang","year":"2017","journal-title":"Food Chem. Toxicol."},{"key":"bfac992abib34","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.ygcen.2014.03.030","article-title":"Reconstruction of a seminiferous tubule-like structure in a 3 dimensional culture system of re-aggregated mouse neonatal testicular cells within a collagen matrix","volume":"205","author":"Zhang","year":"2014","journal-title":"Gen. Comp. 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Sci."}],"container-title":["Biofabrication"],"original-title":[],"link":[{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1758-5090\/ac992a","content-type":"text\/html","content-version":"am","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1758-5090\/ac992a\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1758-5090\/ac992a","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1758-5090\/ac992a\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1758-5090\/ac992a\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1758-5090\/ac992a\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1758-5090\/ac992a\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"similarity-checking"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1758-5090\/ac992a\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T12:46:39Z","timestamp":1666874799000},"score":1,"resource":{"primary":{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1758-5090\/ac992a"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,27]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,10,27]]},"published-print":{"date-parts":[[2023,1,1]]}},"URL":"https:\/\/doi.org\/10.1088\/1758-5090\/ac992a","relation":{},"ISSN":["1758-5082","1758-5090"],"issn-type":[{"value":"1758-5082","type":"print"},{"value":"1758-5090","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,27]]},"assertion":[{"value":"In vitro reconstitution of the hormone-responsive testicular organoids from murine primary testicular cells","name":"article_title","label":"Article Title"},{"value":"Biofabrication","name":"journal_title","label":"Journal Title"},{"value":"paper","name":"article_type","label":"Article Type"},{"value":"\u00a9 2022 The Author(s). Published by IOP Publishing Ltd","name":"copyright_information","label":"Copyright Information"},{"value":"2022-05-09","name":"date_received","label":"Date Received","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2022-10-11","name":"date_accepted","label":"Date Accepted","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2022-10-27","name":"date_epub","label":"Online publication date","group":{"name":"publication_dates","label":"Publication dates"}}]}}