{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T21:18:14Z","timestamp":1793395094342,"version":"4.5.0"},"reference-count":34,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T00:00:00Z","timestamp":1782000000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T00:00:00Z","timestamp":1782000000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82401865 82501944"],"award-info":[{"award-number":["82401865 82501944"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Nonobstructive azoospermia (NOA) is the most severe form of male infertility, with genetic factors contributing to approximately 30% of cases. However, only a small fraction of all NOA cases can be explained by the current genetic findings. ZZS complex participates in meiotic recombination and is necessary for spermatogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To expand the variant spectrum of ZZS complex\u2010associated genes in male infertility and validate the pathogenicity of identified variants in patients with NOA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials\/Methods<\/jats:title>\n                    <jats:p>\n                      A total of 108 Chinese NOA patients were recruited, whole\u2010exome sequencing (WES) and subsequent genetic analysis were performed to identify candidate pathogenic variants. Reverse\u2010transcript PCR (RT\u2010PCR) and quantitative reverse\u2010transcript PCR (RT\u2010qPCR) were performed to detect the mRNA expression of\n                      <jats:italic>TEX11<\/jats:italic>\n                      and\n                      <jats:italic>M1AP<\/jats:italic>\n                      . Hematoxylin and eosin staining and immunofluorescence staining were performed on testicular sections obtained from patients\u2019 biopsies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Five variants in ZZS complex\u2010associated genes\n                      <jats:italic>TEX11<\/jats:italic>\n                      and\n                      <jats:italic>M1AP<\/jats:italic>\n                      were identified from five NOA patients. These variants were either rare or absent in public human genetic databases and were predicted to be deleterious. Further functional analysis revealed that the mRNA expression levels of\n                      <jats:italic>TEX11<\/jats:italic>\n                      and\n                      <jats:italic>M1AP<\/jats:italic>\n                      were significantly reduced in four of the affected patients. Hematoxylin and eosin staining revealed the loss of postmeiosis cells in seminiferous tubules of these patients. Immunofluorescence staining further confirmed the loss of spermatids and the zygotene arrest of meiosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion and Conclusion<\/jats:title>\n                    <jats:p>Collectively, our findings provide compelling evidence for the pathogenicity of these five variants in the development of NOA. These results not only expand the genetic landscape of NOA but also offer valuable insights for future clinical screening and diagnostic strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/andr.70291","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T06:38:10Z","timestamp":1782110290000},"page":"1847-1858","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Variants in ZZS Complex\u2010Associated Genes\n                    <i>TEX11<\/i>\n                    and\n                    <i>M1AP<\/i>\n                    Are Responsible for Male Infertility and Nonobstructive Azoospermia"],"prefix":"10.1111","volume":"14","author":[{"given":"Ao","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Andrology Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urology &amp; Andrology Sir Run Run Shaw Hospital, Zhejiang University School of Medicine  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengwei","family":"Ke","sequence":"additional","affiliation":[{"name":"Department of Urology &amp; Andrology Sir Run Run Shaw Hospital, Zhejiang University School of Medicine  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziqi","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Urology &amp; Andrology Sir Run Run Shaw Hospital, Zhejiang University School of Medicine  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Andrology Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiran","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Andrology Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Andrology Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lv","family":"Yao","sequence":"additional","affiliation":[{"name":"Assisted Reproduction Unit, Department of Obstetrics and Gynecology Sir Run Run Shaw Hospital, Zhejiang University School of Medicine  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuxing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Assisted Reproduction Unit, Department of Obstetrics and Gynecology Sir Run Run Shaw Hospital, Zhejiang University School of Medicine  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feifei","family":"Kong","sequence":"additional","affiliation":[{"name":"Assisted Reproduction Unit, Department of Obstetrics and Gynecology Sir Run Run Shaw Hospital, Zhejiang University School of Medicine  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0660-2048","authenticated-orcid":false,"given":"Lingying","family":"Jiang","sequence":"additional","affiliation":[{"name":"Assisted Reproduction Unit, Department of Obstetrics and Gynecology Sir Run Run Shaw Hospital, Zhejiang University School of Medicine  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6339-6355","authenticated-orcid":false,"given":"Xiaozhi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Andrology Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2234-1080","authenticated-orcid":false,"given":"Beibei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Urology &amp; Andrology Sir Run Run Shaw Hospital, Zhejiang University School of Medicine  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(16)30040-7"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmaa034"},{"issue":"12","key":"e_1_2_9_4_1","first-page":"8185","article-title":"A Novel Homozygous Mutation in the Meiotic Gene MSH4 Leading to Male Infertility due to Non\u2010Obstructive Azoospermia","volume":"12","author":"Tang D.","year":"2020","journal-title":"American Journal of Translational Research"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12958-022-00900-x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00710-4"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23126522"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12958-021-00815-z"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deac092"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41421-023-00577-5"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41421-023-00580-w"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.83"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1273"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aau9780"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.202255778"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007381"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201404967"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12881-018-0570-4"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.4103\/aja.aja_8_21"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1159723"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1406192"},{"key":"e_1_2_9_22_1","volume-title":"WHO Laboratory Manual for the Examination and Processing of Human Semen","author":"World Health Organization","year":"2021"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107524.110"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq603"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btl646"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.107193"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1097\/JU.0000000000001521"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2012.04.048"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2020-107042"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gaac015"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44321-025-00244-0"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2020.06.010"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13712"}],"container-title":["Andrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/andr.70291","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/andr.70291","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/andr.70291","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T04:49:27Z","timestamp":1791434967000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/andr.70291"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,21]]},"references-count":34,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1111\/andr.70291"],"URL":"https:\/\/doi.org\/10.1111\/andr.70291","archive":["Portico"],"relation":{},"ISSN":["2047-2919","2047-2927"],"issn-type":[{"value":"2047-2919","type":"print"},{"value":"2047-2927","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,21]]},"assertion":[{"value":"2025-09-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}