title: Over expression of insulin-like 3 does not prevent cryptorchidism in GNRHR or HOXA10 deficient mice.
abstract: OBJECTIVE
  Insulin-like 3 hormone is critical for the induction of growth and differentiation of gubernacular ligaments during embryonic testicular descent. Mice with mutation of insulin-like 3 or its receptor show high intra-abdominal cryptorchidism. We tested whether transgenic over expression of Insl3 can reverse inguinoscrotal cryptorchidism in mice deficient in Gnrhr or Hoxa10 genes.
  
  
  METHODS
  Hoxa10 and Gnrhr deficient mice were intercrossed with Insl3 transgenic mice. The phenotype of the mutant mice and expression of the genes involved in testicular descent were analyzed. Using quantitative reverse transcriptase-polymerase chain reaction we evaluated expression of the genes in neonatal gubernacular cells on INSL3 (Phoenix Pharmaceuticals, Belmont, California) and testosterone stimulation.
  
  
  RESULTS
  Transgenic over expression of Insl3 failed to restore normal testicular descent in Hoxa10 or Gnrhr deficient males. Histological evaluation did not reveal any differences in Insl3 transgenic gubernacula in either mutant. In mutant females Insl3 over expression resulted in transabdominal descent of the ovaries to the low abdominal position with the subsequent development of inguinal hernia. Expression of androgen receptor, insulin-like 3 receptor and Hoxa10 was not affected after incubation of neonatal gubernacular cells with insulin-like 3 or androgen.
  
  
  CONCLUSIONS
  The results suggest that insulin-like 3 is sufficient to direct the first transabdominal phase of testicular descent in the absence of hypothalamic-pituitary-gonadal axis signaling or Hoxa10 but their presence is important for inguinoscrotal testicular descent.
authors.affiliation: Department of Obstetrics and Gynecology, Baylor College of Medicine, 6550 Fannin Street, Houston, TX 77030, USA.
authors.forename: Shu
authors.initials: S
authors.lastname: Feng
authors.forename: Natalia V
authors.initials: NV
authors.lastname: Bogatcheva
authors.forename: Anne
authors.initials: A
authors.lastname: Truong
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Engel
authors.forename: Ibrahim M
authors.initials: IM
authors.lastname: Adham
authors.forename: Alexander I
authors.initials: AI
authors.lastname: Agoulnik
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D003456:Cryptorchidism / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005260:Female; D015870:Gene Expression; D005801:Genes, Homeobox; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins / Q000235:genetics*; D006728:Hormones / Q000378:metabolism / Q000502:physiology; D007328:Insulin / Q000378:metabolism* / Q000502:physiology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D010053:Ovary / Q000196:embryology; D011506:Proteins / Q000378:metabolism* / Q000502:physiology; D011966:Receptors, LHRH / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013737:Testis / Q000196:embryology / Q000473:pathology
chemical_list: D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; D006728:Hormones; D007328:Insulin; C084797:Leydig insulin-like protein; D011506:Proteins; D011966:Receptors, LHRH; C092119:Hoxa10 protein, mouse