{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T22:43:03Z","timestamp":1791240183907,"version":"4.1.0"},"reference-count":37,"publisher":"The Endocrine Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1999,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The sexual dimorphic position of the gonads in mammals is dependent on differential development of two ligaments, the cranial suspensory ligament (CSL) and the gubernaculum. During male embryogenesis, outgrowth of the gubernaculum and regression of the CSL result in transabdominal descent of the testes, whereas in the female, development of the CSL in conjunction with failure of the gubernaculum development holds the ovaries in a position lateral to the kidneys. Several lines of evidence suggest that regression of the CSL and induction of gubernaculum development are mediated by testosterone and a yet unidentified testicular factor, respectively. The Insl3 gene (orginally designated Ley I-L), a member of the insulin-like superfamily, is specifically expressed in Leydig cells of the fetal and postnatal testis and in theca cells of the postnatal ovary. Here we show that male mice homozygous for a targeted deletion of the Insl3 locus exhibit bilateral cryptorchidism with free moving testes and genital ducts. These malformations are due to failure of gubernaculum development during embryogenesis. In double-mutant male mice for Insl3 and androgen receptor genes, testes are positioned adjacent to the kidneys and steadied in the abdomen by the CSL. These findings demonstrate, that the Insl3 induces gubernaculum development in an androgen-independent way, while androgen-mediated regression of the CSL occurs independently from Insl3.<\/jats:p>","DOI":"10.1210\/mend.13.5.0272","type":"journal-article","created":{"date-parts":[[2014,1,8]],"date-time":"2014-01-08T12:30:35Z","timestamp":1389184235000},"page":"681-691","source":"Crossref","is-referenced-by-count":609,"title":["Targeted Disruption of the Insl3 Gene Causes Bilateral Cryptorchidism"],"prefix":"10.1210","volume":"13","author":[{"given":"Stephan","family":"Zimmermann","sequence":"first","affiliation":[{"name":"Institut fu\u0308r Humangenetik der Universita\u0308t Go\u0308ttingen (S.Z., K.N., W.E., I.M.A.) D-37073 Go\u0308ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerd","family":"Steding","sequence":"additional","affiliation":[{"name":"Abteilung Embryologie der Universita\u0308t Go\u0308ttingen (G.S.) D-37075 Go\u0308ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith M. A.","family":"Emmen","sequence":"additional","affiliation":[{"name":"Endocrinology and Reproduction (J.M.A.E., A.O.B.) Erasmus University Rotterdam N-3000 DR Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert O.","family":"Brinkmann","sequence":"additional","affiliation":[{"name":"Endocrinology and Reproduction (J.M.A.E., A.O.B.) Erasmus University Rotterdam N-3000 DR Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karim","family":"Nayernia","sequence":"additional","affiliation":[{"name":"Institut fu\u0308r Humangenetik der Universita\u0308t Go\u0308ttingen (S.Z., K.N., W.E., I.M.A.) D-37073 Go\u0308ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adolf F.","family":"Holstein","sequence":"additional","affiliation":[{"name":"Abteilung fu\u0308r Mikroskopische Anatomie (A.E.H.) Universita\u0308t-Krankenhaus Eppendorf D-20251 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Engel","sequence":"additional","affiliation":[{"name":"Institut fu\u0308r Humangenetik der Universita\u0308t Go\u0308ttingen (S.Z., K.N., W.E., I.M.A.) D-37073 Go\u0308ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim M.","family":"Adham","sequence":"additional","affiliation":[{"name":"Institut fu\u0308r Humangenetik der Universita\u0308t Go\u0308ttingen (S.Z., K.N., W.E., I.M.A.) D-37073 Go\u0308ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071614145346900_R1","first-page":"379","article-title":"Problems of fetal endocrinology: the gonadal and hypophysial hormones.","volume":"8","author":"Jost","year":"1953","journal-title":"Recent Prog Horm Res"},{"key":"2020071614145346900_R2","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1093\/humupd\/2.5.399","article-title":"Development, structure and function of the cranial suspensory ligaments of the mammalian gonads in a cross-species perspective; their possible role in effecting disturbed testicular descent.","volume":"2","author":"Schoot","year":"1996","journal-title":"Hum Reprod Update"},{"key":"2020071614145346900_R3","first-page":"259","article-title":"Anatomical and functional aspects of testicular descent and cryptorchidism.","volume":"18","author":"Hutson","year":"1997","journal-title":"Endocr Rev"},{"key":"2020071614145346900_R4","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1093\/humrep\/13.5.1272","article-title":"Androgen action during male sex differentiation includes suppression of cranial suspensory ligament development.","volume":"13","author":"Emmen","year":"1998","journal-title":"Hum Reprod"},{"key":"2020071614145346900_R5","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0022-3468(86)80830-2","article-title":"Testicular feminization: a model for testicular descent in mice and men.","volume":"21","author":"Hutson","year":"1986","journal-title":"J Pediatr Surg"},{"key":"2020071614145346900_R6","doi-asserted-by":"crossref","first-page":"2373","DOI":"10.1093\/nar\/19.9.2373","article-title":"A frame-shift mutation in the androgen receptor gene causes complete androgen insensitivity in the testicular feminized mouse.","volume":"19","author":"He","year":"1991","journal-title":"Nucleic Acids Res"},{"key":"2020071614145346900_R7","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1002\/j.1939-4640.1992.tb00349.x","article-title":"Androgen-induced prevention of the outgrowth of cranial gonadal suspensory ligaments in fetal rats.","volume":"13","author":"Schoot","year":"1992","journal-title":"J Androl"},{"key":"2020071614145346900_R8","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1002\/jez.1400230208","article-title":"The freemartin: a study of the action of sex hormones in the foetal life of cattle.","volume":"23","author":"Lillie","year":"1917","journal-title":"J Exp Zool"},{"key":"2020071614145346900_R9","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1002\/ar.1092410208","article-title":"Development of the gubernaculum and processus vaginalis in freemartinism: further evidence in support of a specific fetal testis hormone governing male-specific gubernacular development.","volume":"241","author":"Schoot","year":"1995","journal-title":"Anat Rec"},{"key":"2020071614145346900_R10","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1242\/dev.118.4.1327","article-title":"Foetal testes control the prenatal growth and differentiation of the gubernaculum cones in rabbits \u2014 a tribute to the late Professor Alfred Jost.","volume":"118","author":"Schoot","year":"1993","journal-title":"Development"},{"key":"2020071614145346900_R11","first-page":"179","article-title":"Mu\u0308llerian inhibiting substance. 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