{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:53:30Z","timestamp":1776128010041,"version":"3.50.1"},"reference-count":24,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,2,28]],"date-time":"2017-02-28T00:00:00Z","timestamp":1488240000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"None"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Reproduction Devel"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:title>SUMMARY<\/jats:title><jats:sec><jats:label\/><jats:p>Idiopathic nonobstructive azoospermia (INOA) is one of the most severe forms of male infertility, yet its pathophysiology remains unclear. <jats:italic>WT1<\/jats:italic> (Wilms\u2019 tumor 1) regulates the polarity of Sertoli cells, thereby playing a critical, indirect role in spermatogenesis. Here, we evaluated <jats:italic>WT1<\/jats:italic> gene variation associates with INOA by assessing its promoter and coding regions in 200 patients diagnosed with INOA and 200 proven\u2010fertile men. Three novel variants in the <jats:italic>WT1<\/jats:italic> coding region were detected only in INOA patients, including two synonymous variants and one missense variant, p.Phe435Leu (p.F435L), which was predicted to be deleterious to protein function. The results of dual luciferase reporter showed that the <jats:italic>WT1<\/jats:italic> p.F435L variant decreases transcription of <jats:italic>COL4A1<\/jats:italic> and <jats:italic>WNT4<\/jats:italic> promoters through a dominant\u2010negative effect. Furthermore, chromatin immunoprecipitation assays revealed that <jats:italic>COL4A1<\/jats:italic> and <jats:italic>WNT4<\/jats:italic> promoter is directly bound by wild\u2010type WT1 protein, but not the p.F435L WT1 variant. Thus, we identified a novel functional variant of <jats:italic>WT1<\/jats:italic> functionally associated with INOA. <jats:italic>Mol. Reprod. Dev. 84: 222\u2013228, 2017. \u00a9 2017 Wiley Periodicals, Inc<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mrd.22768","type":"journal-article","created":{"date-parts":[[2016,12,19]],"date-time":"2016-12-19T07:32:43Z","timestamp":1482132763000},"page":"222-228","source":"Crossref","is-referenced-by-count":17,"title":["A novel functional variant in Wilms\u2019 Tumor 1 (<i>WT1<\/i>) is associated with idiopathic non\u2010obstructive azoospermia"],"prefix":"10.1002","volume":"84","author":[{"given":"Jin","family":"Xu","sequence":"first","affiliation":[{"name":"Reproductive Medical Center The Henan Province People's Hospital Zhengzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lile","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology The Second Affiliated Hospital of Zhengzhou University Zhengzhou 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