{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T15:00:50Z","timestamp":1790780450588,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,11,27]],"date-time":"2017-11-27T00:00:00Z","timestamp":1511740800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["15K10642"],"award-info":[{"award-number":["15K10642"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Histone H3.5 (H3.5) is a newly identified histone variant highly expressed in the human testis. We have reported the crystal structure, instability of the H3.5 nucleosome and accumulation around transcription start sites, mainly in primary spermatocytes, but its role in human spermatogenesis remains poorly understood. Testicular biopsy specimens from 30 men (mean age: 35\u00a0years) with non\u2010obstructive azoospermia (<jats:styled-content style=\"fixed-case\">NOA<\/jats:styled-content>) who underwent microdissection testicular sperm extraction and 23 men with obstructive azoospermia (<jats:styled-content style=\"fixed-case\">OA<\/jats:styled-content>) were included. An H3.5\u2010specific mouse monoclonal antibody recognizing an H3.5\u2010specific synthetic peptide was generated, and immunohistological staining for H3.5 and proliferating cell nuclear antigen (<jats:styled-content style=\"fixed-case\">PCNA<\/jats:styled-content>) was performed on Bouin's solution\u2010fixed sections. Expression and localization of H3.5 were compared with patient background, germinal stage, and <jats:styled-content style=\"fixed-case\">PCNA<\/jats:styled-content> expression. In testes of patients with normal spermatogenesis, differentially expressed H3.5 was specifically localized in either spermatogonia or preleptotene\/leptotene\u2010stage primary spermatocytes, especially during germinal stages VI\u2013X. In <jats:styled-content style=\"fixed-case\">NOA<\/jats:styled-content> testes, <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> expression of H3.5 (<jats:italic>H3F3C<\/jats:italic>) was significantly reduced compared with other H3 histone family members, and expression of H3.5 was significantly lower than that in <jats:styled-content style=\"fixed-case\">OA<\/jats:styled-content>. Additionally, the number of H3.5\u2010positive germ cells was higher in hypospermatogenesis or late maturation arrest than in early maturation arrest in <jats:styled-content style=\"fixed-case\">NOA<\/jats:styled-content> testes (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.01). A significant positive correlation was observed between H3.5 and <jats:styled-content style=\"fixed-case\">PCNA<\/jats:styled-content> expression (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05) but not <jats:styled-content style=\"fixed-case\">TUNEL<\/jats:styled-content>\u2010positive cells, and expression of H3.5 was enhanced after <jats:styled-content style=\"fixed-case\">hCG<\/jats:styled-content>\u2010based salvage hormonal therapy. Different from other testis\u2010specific histones, which are often expressed during the histone\u2010to\u2010protamine transition during meiosis, H3.5 was expressed mainly in immature germ cells. H3.5 may play roles in <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> synthesis, but not apoptosis, and its expression is regulated by gonadotropins, indicating that such epigenetic regulations are important in normal spermatogenesis and spermatogenic disorders.<\/jats:p>","DOI":"10.1111\/andr.12438","type":"journal-article","created":{"date-parts":[[2017,11,27]],"date-time":"2017-11-27T22:08:58Z","timestamp":1511820538000},"page":"158-165","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Roles of histone H3.5 in human spermatogenesis and spermatogenic disorders"],"prefix":"10.1111","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3278-7747","authenticated-orcid":false,"given":"K.","family":"Shiraishi","sequence":"first","affiliation":[{"name":"Department of Urology Yamaguchi University School of Medicine Ube Yamaguchi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Shindo","sequence":"additional","affiliation":[{"name":"Department of Urology Yamaguchi University School of Medicine Ube Yamaguchi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Harada","sequence":"additional","affiliation":[{"name":"Division of Transcriptomics Medical Institute of Bioregulation Kyushu University Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Kurumizaka","sequence":"additional","affiliation":[{"name":"Laboratory of Structural Biology Graduate School of Advanced Science and Engineering Waseda University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Kimura","sequence":"additional","affiliation":[{"name":"Cell Biology Unit Institute of Innovative Research Tokyo Institute of Technology Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Ohkawa","sequence":"additional","affiliation":[{"name":"Division of Transcriptomics Medical Institute of Bioregulation Kyushu University Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Matsuyama","sequence":"additional","affiliation":[{"name":"Department of Urology Yamaguchi University School of Medicine Ube Yamaguchi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,11,27]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-0436.1997.6210013.x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2009.07504.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1346"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.110.088955"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2047-2927.2014.00240.x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.4161\/epi.3.1.5555"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03368"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2007.05.068"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep08785"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.066845"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.f.1895"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.136.9.4035"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1939-4640.1999.tb03382.x"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06236"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1387\/ijdb.082653go"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00542-6"},{"key":"e_1_2_8_18_1","volume-title":"Histological 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