{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T08:32:44Z","timestamp":1769070764154,"version":"3.49.0"},"reference-count":44,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2020,6,8]],"date-time":"2020-06-08T00:00:00Z","timestamp":1591574400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870459"],"award-info":[{"award-number":["81870459"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81970572"],"award-info":[{"award-number":["81970572"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The aberrant expression of genes involved in androgen metabolism and genetic contribution are unclear in hypospadias.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We compared gene expression profiles by RNA sequencing from five non\u2010hypospadiac foreskins, five mild hypospadiac foreskins, and five severe hypospadiac foreskins. In addition, to identify rare coding variants with large effects on hypospadias risk, we carried out whole exome sequencing in three patients in a hypospadias family.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The average expression of androgen receptor (<jats:italic>AR<\/jats:italic>) and <jats:italic>CYP19A1<\/jats:italic> were significantly decreased in severe hypospadias (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.01) and mild hypospadias (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.05), whereas expression of several other androgen metabolism enzymes, including <jats:italic>CYP3A4<\/jats:italic>, <jats:italic>HSD17B14<\/jats:italic>, <jats:italic>HSD3B7<\/jats:italic>, <jats:italic>HSD17B7<\/jats:italic>, <jats:italic>CYP11A1<\/jats:italic> were exclusively significantly expressed in severe hypospadias (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.05). Compound rare damaging mutants of <jats:italic>AR<\/jats:italic> gene with <jats:italic>HSD3B1<\/jats:italic> and <jats:italic>SLC25A5<\/jats:italic> genes were identified in the different severe hypospadias.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In conclusion, our findings demonstrated that dysregulation of <jats:italic>AR<\/jats:italic> and <jats:italic>CYP19A1<\/jats:italic> could play a crucial role in the development of hypospadias. Inconsistent <jats:italic>AR<\/jats:italic> expression may be caused by the feedback loop of ESR1 signaling or combined genetic effects with other risk genes. This findings complement the possible role of <jats:italic>AR<\/jats:italic> triggered mechanism in the development of hypospadias.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1346","type":"journal-article","created":{"date-parts":[[2020,6,9]],"date-time":"2020-06-09T02:39:06Z","timestamp":1591670346000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Dysregulated expression of androgen metabolism genes and genetic analysis in hypospadias"],"prefix":"10.1002","volume":"8","author":[{"given":"Zhongzhong","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Urology Shanghai Children\u2019s Hospital Shanghai Jiao Tong University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoling","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Urology Huashan Hospital Fudan University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaping","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urology Shanghai Children\u2019s Hospital Shanghai Jiao Tong University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Urology Shanghai Children\u2019s Hospital Shanghai Jiao Tong University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2298-2610","authenticated-orcid":false,"given":"Fang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Urology Shanghai Children\u2019s Hospital Shanghai Jiao Tong University Shanghai China"},{"name":"Department of Urology Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital Shanghai China"},{"name":"Shanghai Eastern Urological Reconstruction and Repair Institute Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,6,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410\u2010248"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.4103\/jiaps.JIAPS_166_18"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1159\/000441988"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2047\u20102927.2013.00165.x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.14744\/nci.2018.47108"},{"issue":"6","key":"e_1_2_9_7_1","first-page":"1784","article-title":"Joint effect of HSD3B1 and HSD3B2 genes is associated with hereditary and sporadic prostate cancer susceptibility","volume":"62","author":"Chang B. 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