{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T23:35:40Z","timestamp":1788305740593,"version":"build-2803163510"},"reference-count":22,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,3,12]],"date-time":"2013-03-12T00:00:00Z","timestamp":1363046400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2013,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>A significant number of patients with germline mutations in the Wilms' tumour 1 (<jats:italic> <jats:styled-content style=\"fixed-case\">WT1<\/jats:styled-content><\/jats:italic>) gene, a transcriptional factor essential for early renal and gonadal development, display cryptorchidism or non\u2010scrotal testis position. We show here that <jats:styled-content style=\"fixed-case\">WT1<\/jats:styled-content> is expressed during development in the mouse gubernacular ligament connecting the testis to the abdominal wall. Conditional inactivation of <jats:italic>Wt1<\/jats:italic> in the gubernaculum (<jats:styled-content style=\"fixed-case\">GU\u2010WT1KO<\/jats:styled-content> animals) resulted in abnormal differentiation of the gubernacula during development and, in about 40% of adult males, unilateral, always left\u2010sided, cryptorchidism. At birth the right testis was positioned above the processus vaginalis and eventually moved into the developing scrotal pouch. In affected mutants the left testis was displaced from the normal position and the left processus vaginalis failed to form. The analysis of testicular descent at different stages of postnatal development suggests that unilateral cryptorchidism might be caused by asymmetry in the positions of the abdominal organs providing a higher degree of mobility for the left testis. Spermatogenesis in <jats:styled-content style=\"fixed-case\">GU\u2010WT1KO<\/jats:styled-content> animals was blocked in cryptorchid testes located in a high pararenal position, but was maintained in testes located in a low abdominal position. Conditional inactivation of both <jats:italic>Wt1<\/jats:italic> and androgen receptor (<jats:italic>Ar<\/jats:italic>) genes in the gubernaculum led to a bilateral asymmetrical cryptorchidism in all mutant males, with the left testis again located higher than the right one. The malformations induced by <jats:styled-content style=\"fixed-case\">WT1<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content> deficiency in the gubernaculum and processus vaginalis, in combination with mechanical constraints on testis descent, determine the final position of the testes. In summary, our data indicate that <jats:styled-content style=\"fixed-case\">WT1<\/jats:styled-content> is directly involved in gubernaculum differentiation. Taken together, the results of the study underline the complex nature of testicular descent, with an involvement in this process of several genetic factors and developmental events. Copyright \u00a9 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:bold><\/jats:p>","DOI":"10.1002\/path.4161","type":"journal-article","created":{"date-parts":[[2013,1,3]],"date-time":"2013-01-03T09:40:38Z","timestamp":1357206038000},"page":"39-47","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Left\u2010sided cryptorchidism in mice with Wilms' tumour 1 gene deletion in gubernaculum testis"],"prefix":"10.1002","volume":"230","author":[{"given":"Elena M","family":"Kaftanovskaya","sequence":"first","affiliation":[{"name":"Department of Human and Molecular Genetics, Herbert Wertheim College of Medicine Florida International University  Miami FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giselle","family":"Neukirchner","sequence":"additional","affiliation":[{"name":"Department of Human and Molecular Genetics, Herbert Wertheim College of Medicine Florida International University  Miami FL 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