title: Molecular signals governing cremaster muscle development: clues for cryptorchidism.
abstract: OBJECTIVE
  Cryptorchidism affects 2-4% of newborn boys. Testicular descent requires the gubernaculum to differentiate into cremaster muscle (CM) during androgen-mediated inguino-scrotal descent, but the cellular mechanisms regulating this remodeling remain elusive. β-Catenin, a marker of canonical Wnt signaling, promotes myogenic genes and cellular adhesion. We aimed to determine if androgen receptor (AR) blockade altered β-catenin and its downstream myogenic proteins within the CM.
  
  
  METHODS
  Gubernacula from male rats (n=12) and rats treated with anti-androgen, flutamide (n=12) at E19, D0, D2 were processed for immunohistochemistry. Antibodies against β-catenin, embryonic myosin, and myogenin were visualized by confocal microscopy.
  
  
  RESULTS
  At E19, β-catenin immuno-reactivity (IR) localized to the CM membrane. By D2, cytoplasmic β-catenin-IR was noted with overall β-catenin-IR decreasing. Myogenic proteins resided primarily in cells containing β-catenin on their plasma membrane. Embryonic myosin-IR was high at E19 and then decreased by D2, while myogenin-IR increased. AR blockade increased cytoplasmic β-catenin at D2 and reduced levels of both myogenic proteins.
  
  
  CONCLUSIONS
  Myogenic proteins are present in CM cells containing β-catenin. AR blockade did not alter cellular adhesion via β-catenin. In contrast, blocking AR prevented β-catenin entering the nucleus and impaired CM myogenesis. Mutations in this pathway may result in idiopathic cryptorchidism.
authors: Douglas Stephens Surgical Research Group, Murdoch Children's Research Institute, Melbourne, Australia; Department of Anatomy and Neuroscience, University of Melbourne, Australia.
authors: Maciej
authors: M
authors: Szarek
authors: Douglas Stephens Surgical Research Group, Murdoch Children's Research Institute, Melbourne, Australia.
authors: Ruili
authors: R
authors: Li
authors: Douglas Stephens Surgical Research Group, Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Australia.
authors: Jaya
authors: J
authors: Vikraman
authors: Douglas Stephens Surgical Research Group, Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Australia.
authors: Bridget
authors: B
authors: Southwell
authors: Douglas Stephens Surgical Research Group, Murdoch Children's Research Institute, Melbourne, Australia; Department of Anatomy and Neuroscience, University of Melbourne, Australia; Department of Paediatrics, University of Melbourne, Australia; Urology Department, Royal Children's Hospital, Melbourne, Australia. Electronic address: john.hutson@rch.org.au.
authors: John M
authors: JM
authors: Hutson
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D003456:Cryptorchidism / Q000378:metabolism*; D005485:Flutamide / Q000494:pharmacology; D007150:Immunohistochemistry; D008022:Ligaments / Q000254:growth & development* / Q000378:metabolism*; D008297:Male; D018613:Microscopy, Confocal; D024510:Muscle Development; D018008:Myogenin / Q000378:metabolism; D009218:Myosins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D018008:Myogenin; D051176:beta Catenin; D005485:Flutamide; D009218:Myosins
keywords: Beta-catenin; Cremaster muscle; Cryptorchidism; Differentiation; Gubernaculums; Testes; Wnt signaling