{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,4]],"date-time":"2026-01-04T23:16:21Z","timestamp":1767568581447,"version":"3.48.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"6","funder":[{"DOI":"10.13039\/501100018534","name":"Medical Innovation Project of Fujian Province","doi-asserted-by":"crossref","award":["2023CXA016"],"award-info":[{"award-number":["2023CXA016"]}],"id":[{"id":"10.13039\/501100018534","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["rep.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,10,15]]},"abstract":"<jats:sec>\n                    <jats:title>In brief<\/jats:title>\n                    <jats:p>\n                      Non-obstructive azoospermia (NOA) is a major cause of male infertility, with many cases having unknown origins. This study identifies two\n                      <jats:italic>TOP6BL<\/jats:italic>\n                      variants linked to NOA, revealing their impact on meiotic DNA double-strand break (DSB) formation and spermatogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Azoospermia, particularly NOA, affects approximately 1% of men and accounts for 10\u201320% of male infertility cases, with a substantial proportion of NOA cases remaining of unknown aetiology. This study investigated the role of the\n                      <jats:italic>TOP6BL<\/jats:italic>\n                      gene in NOA in two consanguineous Han Chinese families. Two distinct variants in\n                      <jats:italic>TOP6BL<\/jats:italic>\n                      , c.1067C&gt;G:p.Pro356Arg and c.1543C&gt;T:p.Arg515Ter (NM_024650.3 \u2192 NP_078926.3), were identified, both linked to NOA in these families. These variants disrupted meiotic DNA DSB formation, an essential process in spermatogenesis, resulting in meiotic arrest at the zygotene stage. Functional analyses revealed that the p.Arg515Ter variant impaired binding to REC114 and disrupted interaction with SPO11, whereas the p.Pro356Arg variant did not affect protein binding but impaired self-dimerisation. Moreover, deletion of the\n                      <jats:italic>TOP6BL<\/jats:italic>\n                      central region in mice induced meiotic arrest, confirming the critical role of this region in spermatogenesis. These results highlight the diverse mechanisms by which\n                      <jats:italic>TOP6BL<\/jats:italic>\n                      variants contribute to NOA and highlight the pivotal role of the\n                      <jats:italic>TOP6BL<\/jats:italic>\n                      intermediate region. Thus, disruption of meiotic DSB formation is a key mechanism underlying male infertility.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/rep-25-0298","type":"journal-article","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T14:59:41Z","timestamp":1760540381000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-11","source":"Crossref","is-referenced-by-count":0,"title":["Mechanisms of non-obstructive azoospermia caused by TOP6BL variants"],"prefix":"10.1093","volume":"170","author":[{"given":"Chao","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Andrology and Sexual Medicine, First Affiliated Hospital of Fujian Medical University, Fuzhou, China"},{"name":"Key Laboratory of Stem Cell Engineering and Regenerative Medicine of Fujian Province University, Fujian Medical University, Fuzhou, China"},{"name":"Xianyang Central Hospital, Xianyang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanwei","family":"Sha","sequence":"additional","affiliation":[{"name":"Department of Andrology, Women and Children\u2019s Hospital, School of Medicine, Xiamen University, Xiamen, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yayun","family":"Ji","sequence":"additional","affiliation":[{"name":"Xianyang Central Hospital, Xianyang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peilin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, First Affiliated Hospital of Fujian Medical University, Fuzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1355-2475","authenticated-orcid":true,"given":"Shie","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Stem Cell Engineering and Regenerative Medicine of Fujian Province University, Fujian Medical University, Fuzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7154-3657","authenticated-orcid":true,"given":"Huiliang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Andrology and Sexual Medicine, First Affiliated Hospital of Fujian Medical University, Fuzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","reference":[{"key":"bib1","series-title":"Nucleic Acids Res","first-page":"755","article-title":"Solution structures of DNA-bound gyrase","volume":"39","author":"Baker NM","year":"2011","unstructured":"Baker NM\n, \nWeigand S\n, \nMaar-Mathias S\n, et al.\n 2011 Solution structures of DNA-bound gyrase. 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