title: Loss of Insl3: a potential predisposing factor for testicular torsion.
abstract: OBJECTIVE
  The testicular hormone Insl3 is critical for mouse gubernacular development. Knockout mice exhibit bilateral intra-abdominal cryptorchidism with absent gubernaculum. Prior studies described torsion of the vas deferens in Insl3 mutant mice. We performed a detailed anatomical analysis of the vas deferens and testis in Insl3 mutant mice to characterize associated anomalies further.
  
  
  METHODS
  Insl3 wild-type (Insl3(+/+)), heterozygous (Insl3(+/-)) and knockout (Insl3(-/-)) male mice were examined either prepubertally (postnatal day 23) or in adulthood (postnatal day 90 or later). The macroscopic appearance, characteristics, and mobility of the testes and spermatic cord were recorded.
  
  
  RESULTS
  We examined 56 prepubertal and 33 adult mice (175 testes, 28 [20:8] Insl3(+/+), 97 [60:37] Insl3(+/-), 50 [32:18] Insl3(-/-)). Unlike normal Insl3(+/+) testes, 94% of Insl3(-/-) testes were located intra-abdominally at all ages. Delayed descent occurred in Insl3((+/-)) testes, since 37% of postnatal day 23 and 8% of P90 or later testes were intra-abdominal. Vas elongation/convolution and spermatic cord twisting were noted in 65% of Insl3(-/-), 27% of Insl3((+/-)) and 0% of Insl3(+/+) testes. While all Insl3(+/+) testes were normal, 5% of Insl3((+/-)) and 32% of Insl3(-/-) testes showed significant testicular pathology, including torsion, atrophy and vanished testis, which statistically increased with age.
  
  
  CONCLUSIONS
  Poorly formed gubernacula and increased testicular mobility in Insl3 mutant mice result in spermatic cord anomalies, delayed/absent testicular descent and subsequent testicular torsion in a gene dose dependent manner. Prepubertal testicular torsion in the mutant mice predisposes to testicular atrophy and vanishing testes in adulthood. Thus, Insl3 is a candidate signaling molecule in human delayed testicular descent and torsion.
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9110, USA.
authors.forename: Selami
authors.initials: S
authors.lastname: Sozubir
authors.forename: Theodore
authors.initials: T
authors.lastname: Barber
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Chul
authors.initials: C
authors.lastname: Ahn
authors.forename: Shaohua
authors.initials: S
authors.lastname: Zhang
authors.forename: Sunita
authors.initials: S
authors.lastname: Verma
authors.forename: Devin
authors.initials: D
authors.lastname: Lonergan
authors.forename: Armando J
authors.initials: AJ
authors.lastname: Lorenzo
authors.forename: Serge
authors.initials: S
authors.lastname: Nef
authors.forename: Linda A
authors.initials: LA
authors.lastname: Baker
mesh_terms: D000818:Animals; D020022:Genetic Predisposition to Disease; D007328:Insulin / Q000235:genetics*; D008297:Male; D051379:Mice; D011506:Proteins / Q000235:genetics*; D013086:Spermatic Cord Torsion / Q000235:genetics* / Q000473:pathology*
chemical_list: D007328:Insulin; C084797:Leydig insulin-like protein; D011506:Proteins