title: Wnt signalling in testicular descent: a candidate mechanism for cryptorchidism in Robinow syndrome.
abstract: OBJECTIVE
  Robinow syndrome is caused by mutations in Wnt-5a or its receptor Ror2 and can lead to cryptorchidism, though the mechanisms are unclear. Wnt-5a knock-out mice fail to undergo gubernacular swelling, similar to insulin-like hormone 3 (INSl-3) knock-out mice. We aimed to characterise Wnt-5a and Ror2 expression in rat gubernacula to better understand how Wnt-5a signalling affects testicular descent.
  
  
  METHODS
  Sprague-Dawley rats (n = 27) were collected with ethics approval (A644) at embryonic days (E) 15, 17, 19 and postnatal day (D) 2. Control and antiandrogen-treated groups were processed for immunohistochemistry for Wnt-5a, Ror2 and β-catenin. Sagittal sections were examined using confocal microscopy.
  
  
  RESULTS
  Wnt-5a and Ror2 were strongly expressed in the gubernacular bulb at E17 controls, their levels declining at E19 and almost absent by D2. Wnt-5a significantly co-localised with the important transcription factor β-catenin at E17. There was no obvious difference in staining with androgen blockade.
  
  
  CONCLUSIONS
  Wnt-5a, through Ror2 and β-catenin may play a vital role in regulating the gubernacular swelling reaction downstream of INSL-3. Human mutations in Wnt-5a or Ror2 could prevent early gubernacular growth, as suggested by undescended testes in 70% of patients with Robinow Syndrome.
authors.affiliation: Douglas Stephens Surgical Research Laboratory, Murdoch Children's Research Institute, Melbourne, Australia.
authors.forename: George N
authors.initials: GN
authors.lastname: Harisis
authors.forename: Nan
authors.initials: N
authors.lastname: Chen
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Farmer
authors.forename: Daniela
authors.initials: D
authors.lastname: Bodemer
authors.forename: Ruili
authors.initials: R
authors.lastname: Li
authors.forename: Magdy
authors.initials: M
authors.lastname: Sourial
authors.forename: Bridget R
authors.initials: BR
authors.lastname: Southwell
authors.forename: Adam
authors.initials: A
authors.lastname: Balic
authors.forename: John M
authors.initials: JM
authors.lastname: Hutson
mesh_terms: D000818:Animals; D019465:Craniofacial Abnormalities / Q000209:etiology*; D003456:Cryptorchidism / Q000209:etiology*; D004392:Dwarfism / Q000209:etiology*; D017880:Limb Deformities, Congenital / Q000209:etiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000096:biosynthesis*; D013737:Testis / Q000254:growth & development*; D014564:Urogenital Abnormalities / Q000209:etiology*; D051153:Wnt Proteins / Q000096:biosynthesis*; D060449:Wnt Signaling Pathway / Q000502:physiology*; D000071818:Wnt-5a Protein
chemical_list: D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C491837:Wnt5a protein, rat; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; C500913:Ror2 protein, rat
keywords: Cryptorchidism; Gubernaculum; Robinow syndrome; Testicular descent; Wnt-5a