{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:15:56Z","timestamp":1787501756056,"version":"build-2736575974"},"reference-count":55,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2024QH501"],"award-info":[{"award-number":["ZR2024QH501"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82301809 82571844"],"award-info":[{"award-number":["82301809 82571844"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFC2705503"],"award-info":[{"award-number":["2023YFC2705503"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019018","name":"Chinese Academy of Medical Sciences Initiative for Innovative Medicine","doi-asserted-by":"publisher","award":["2021\u2010I2M\u20105\u2010001"],"award-info":[{"award-number":["2021\u2010I2M\u20105\u2010001"]}],"id":[{"id":"10.13039\/501100019018","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2026,7]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n Non\u2010obstructive azoospermia (NOA) is a major cause of male infertility, frequently associated with congenital factors. Nevertheless, the genetic underpinnings of NOA remain largely unclear.<\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n \n This study aimed to identify and characterize novel genetic variants contributing to NOA, with a focus on\n TEX14<\/jats:italic>\n , a gene critical for intercellular bridge (ICB) formation during meiosis.\n <\/jats:p>\n <\/jats:sec>\n \n Materials\/Methods<\/jats:title>\n \n Exome sequencing was performed on genomic DNA from a cohort of 673 patients with NOA, 143 individuals with oligozoospermia, and 100 fertile controls. Potentially pathogenic\n TEX14<\/jats:italic>\n variants were identified and confirmed by Sanger sequencing. Functional analysis, including qPCR and Western blot, was performed to assess TEX14 expression levels in patient and mouse testicular samples and the effects of\n TEX14<\/jats:italic>\n variants on spermatogenesis and ICB formation in both mice and humans.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n We identified six novel\n TEX14<\/jats:italic>\n variants in four unrelated infertile Chinese men, including three frameshift mutations (c.2908dupC, p.Arg970Profs5; c.1881dupA, p.Gly628Argfs8; c.1728_1729del, p.Leu577Argfs*58), two missense mutations (c.1121A>G, p.Tyr374Cys; c.865G>A, p.Glu289Lys), and one splicing mutation (c.417+2T>C). To functionally validate the pathogenicity of the frameshift variant c.2908dupC, a mouse model carrying an analogous mutation (\n Tex14<\/jats:italic>\n MT1\/MT1<\/jats:sup>\n ) was generated. These mice recapitulated the human NOA phenotype, showing a complete loss of TEX14 expression in the testis. Immunofluorescence and histological analyses revealed that spermatogenesis in\n Tex14<\/jats:italic>\n MT1\/MT1<\/jats:sup>\n mice was arrested at the zygotene stage due to a complete failure of the ICB formation. Consistent with this, testicular histology from the patient carrying the c.2908dupC variant also showed meiotic arrest at zygotene and absent ICBs. Furthermore, mass spectrometry analysis of purified ICBs indicated that ICB\u2010associated proteins are predominantly involved in RNA processing and ribonucleoprotein complex biogenesis.\n <\/jats:p>\n <\/jats:sec>\n \n Discussion and Conclusion<\/jats:title>\n \n Our results demonstrate that loss\u2010of\u2010function mutations in\n TEX14<\/jats:italic>\n disrupt meiotic ICB formation, leading to zygotene arrest and NOA in both mice and humans, expand the spectrum of pathogenic variants associated with NOA, and establish the essential role of\n TEX14<\/jats:italic>\n in meiotic progression, underscoring the functional importance of\n TEX14<\/jats:italic>\n in male fertility.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/andr.70185","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T14:02:42Z","timestamp":1769608962000},"page":"1355-1371","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pathogenic\n TEX14<\/i>\n Variants Disrupt Intercellular Bridge Formation, Causing Meiotic Arrest and Non\u2010Obstructive Azoospermia in Humans and Mice"],"prefix":"10.1111","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-6040-294X","authenticated-orcid":false,"given":"Jianze","family":"Xu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health Shandong University Jinan China"},{"name":"National Research Center for Assisted Reproductive Technology and Reproductive Genetics Shandong University Jinan Shandong China"},{"name":"Key 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