{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:46:05Z","timestamp":1792788365822,"version":"4.5.0"},"reference-count":0,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Japan Society for the Promotion of Science","award":["JP24K02318"],"award-info":[{"award-number":["JP24K02318"]}],"id":[{"id":"https:\/\/ror.org\/00hhkn466","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Japan Society for the Promotion of Science","award":["JP22H04922"],"award-info":[{"award-number":["JP22H04922"]}],"id":[{"id":"https:\/\/ror.org\/00hhkn466","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Japan Society for the Promotion of Science","award":["JP22H04923"],"award-info":[{"award-number":["JP22H04923"]}],"id":[{"id":"https:\/\/ror.org\/00hhkn466","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Japan Science Society","award":["2023-4040"],"award-info":[{"award-number":["2023-4040"]}],"id":[{"id":"https:\/\/ror.org\/03aeyg892","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>BRD8, a member of the bromodomain-containing protein family, is a chromatin-associated protein that recognizes acetylated histones and recruits regulatory factors to modulate gene expression. Despite extensive studies of BRD8 in tumor biology, its physiological roles in normal tissues remain largely unknown. Given its enriched expression in the testis, we investigated the role of Brd8 in male reproduction using a germ cell-specific Brd8 knockout mouse model. Brd8 deficiency resulted in a marked reduction in testicular size and sperm counts, accompanied by severe defects in germ cell differentiation. Immunofluorescence staining for germ cell markers demonstrated progressive spermatogenic defects, with a reduction in spermatids followed by declines in spermatocytes and spermatogonia at later ages. Single-cell transcriptome analysis of Brd8-knockout testes revealed transcriptional alterations in spermatogonia and spermatocytes, including dysregulation of translation-related pathways and reduced expression of genes involved in meiotic progression. In addition, VEGF-related signaling within the endothelial compartment was reduced in Brd8-knockout testes, suggesting secondary remodeling of the testicular microenvironment associated with progressive germ cell dysfunction. Our findings provide new insights into the role of BRD8, an epigenetic reader, in male fertility.<\/jats:p>","DOI":"10.1242\/jcs.265013","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T09:35:01Z","timestamp":1791452101000},"source":"Crossref","is-referenced-by-count":0,"title":["BRD8 deficiency leads to progressive impairment of spermatogenesis in mice"],"prefix":"10.1242","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5893-1663","authenticated-orcid":false,"given":"Saya","family":"Nakagawa","sequence":"first","affiliation":[{"name":"1 Division of Clinical Genome Research, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3284-7161","authenticated-orcid":false,"given":"Manabu","family":"Ozawa","sequence":"additional","affiliation":[{"name":"2 Core Laboratory for Developing Advanced Animal Models, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan"},{"name":"3 Laboratory of Reproductive Systems Biology, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teh-Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"4 Division of Cancer Cell Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan"},{"name":"5 Project Division of Generative AI Utilization Aging Cells, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuneo","family":"Ikenoue","sequence":"additional","affiliation":[{"name":"1 Division of Clinical Genome Research, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumiko","family":"Isobe","sequence":"additional","affiliation":[{"name":"1 Division of Clinical Genome Research, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eigo","family":"Shimizu","sequence":"additional","affiliation":[{"name":"6 Division of Health Medical Intelligence, Human Genome Center, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6707-3584","authenticated-orcid":false,"given":"Makoto","family":"Nakanishi","sequence":"additional","affiliation":[{"name":"4 Division of Cancer Cell Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2989-308X","authenticated-orcid":false,"given":"Seiya","family":"Imoto","sequence":"additional","affiliation":[{"name":"6 Division of Health Medical Intelligence, Human Genome Center, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0462-8631","authenticated-orcid":false,"given":"Yoichi","family":"Furukawa","sequence":"additional","affiliation":[{"name":"1 Division of Clinical Genome Research, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2113-4369","authenticated-orcid":false,"given":"Kiyoshi","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"1 Division of Clinical Genome Research, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2026,10,8]]},"container-title":["Journal of Cell Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.biologists.com\/jcs\/article-pdf\/doi\/10.1242\/jcs.265013\/3720499\/jcs265013.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/jcs\/article-pdf\/doi\/10.1242\/jcs.265013\/3720499\/jcs265013.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T09:35:02Z","timestamp":1791452102000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/jcs\/article\/doi\/10.1242\/jcs.265013\/373114\/BRD8-deficiency-leads-to-progressive-impairment-of"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,8]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1242\/jcs.265013","relation":{},"ISSN":["0021-9533","1477-9137"],"issn-type":[{"value":"0021-9533","type":"print"},{"value":"1477-9137","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,8]]},"article-number":"jcs.265013"}}