title: Neurotrophin signaling in a genitofemoral nerve target organ during testicular descent in mice.
abstract: OBJECTIVE
  It has been proposed that androgens control inguinoscrotal testicular descent via release of calcitonin gene-related peptide (CGRP) from a masculinised genitofemoral nerve (GFN). As there are androgen receptors in the inguinoscrotal fat pad (IFP) during the window of androgen sensitivity (E14-17 in mouse embryos), we tested the hypothesis that neurotrophins in the IFP may masculinise the sensory fibers of the GFN supplying the gubernaculum and IFP prior to gubernacular migration.
  
  
  METHODS
  Androgen-receptor knockout (ARKO) and wild-type (WT) mouse embryos were collected at E17, with ethical approval (AEC 734). Sagittal sections of IFP, mammary area and bulbocavernosus (BC) muscle were processed for standard histology and fluorescent immunohistochemistry for ciliary neurotrophic factor (CNTF), ciliary neurotrophic factor receptor (CNTFR) and cell nuclei (DAPI).
  
  
  RESULTS
  In the ARKO mouse CNTFR immunoreactivity (CNTFR-IR) was increased in the IFP but decreased in BC. Perinuclear staining of CNTF-IR was seen in mouse sciatic nerve but only weakly in IFP. In the mammary area, also supplied by GFN, there were no differences in IR staining.
  
  
  CONCLUSIONS
  This study found CNTFR-IR in the IFP was negatively regulated by androgen, suggesting that CNTF signaling may be suppressed in GFN sensory nerves to enable CGRP expression for regulating gubernacular migration in the male, but not the female. The indirect action of androgen via the GFN required for testicular descent may be one of the sites of anomalies in the putative multifactorial cause of cryptorchidism.
authors.affiliation: F Douglas Stephens, Surgical Research Group, Murdoch Childrens Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia.
authors.forename: Mary C
authors.initials: MC
authors.lastname: Cousinery
authors.affiliation: F Douglas Stephens, Surgical Research Group, Murdoch Childrens Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia.
authors.forename: Ruili
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Paediatrics, University of Melbourne, Melbourne, Australia.
authors.forename: Amanda
authors.initials: A
authors.lastname: Vannitamby
authors.affiliation: F Douglas Stephens, Surgical Research Group, Murdoch Childrens Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia.
authors.forename: Jaya
authors.initials: J
authors.lastname: Vikraman
authors.affiliation: F Douglas Stephens, Surgical Research Group, Murdoch Childrens Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia.
authors.forename: Bridget R
authors.initials: BR
authors.lastname: Southwell
authors.affiliation: F Douglas Stephens, Surgical Research Group, Murdoch Childrens Research Institute, Melbourne, Australia; Department of Urology, The Royal Children's Hospital, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia. Electronic address: john.hutson@rch.org.au.
authors.forename: John M
authors.initials: JM
authors.lastname: Hutson
mesh_terms: D000728:Androgens / Q000502:physiology; D000818:Animals; D020934:Ciliary Neurotrophic Factor / Q000502:physiology*; D003456:Cryptorchidism / Q000209:etiology / Q000503:physiopathology*; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D020801:Receptor, Ciliary Neurotrophic Factor / Q000502:physiology*; D011944:Receptors, Androgen / Q000502:physiology*; D015398:Signal Transduction; D013737:Testis / Q000294:innervation / Q000502:physiology* / Q000503:physiopathology*
chemical_list: D000728:Androgens; D020934:Ciliary Neurotrophic Factor; D020801:Receptor, Ciliary Neurotrophic Factor; D011944:Receptors, Androgen
keywords: ciliary neurotrophic factor; genitofemoral nerve; neurotrophin; testicular descent