Over Expression of Insulin-Like 3 Does Not Prevent Cryptorchidism in GNRHR or HOXA10 Deficient Mice

Shu Feng, Natalia V. Bogatcheva, Anne Truong, Wolfgang Engel, Ibrahim M. Adham, Alexander I. Agoulnik

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


Purpose: 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. Materials and 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.

Original languageEnglish (US)
Pages (from-to)399-404
Number of pages6
JournalJournal of Urology
Issue number1
StatePublished - Jul 1 2006
Externally publishedYes


  • Leydig insulin-like protein
  • cryptorchidism
  • gene expression
  • mice
  • testis

ASJC Scopus subject areas

  • Urology

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