title: Gonocyte transformation to spermatogonial stem cells occurs earlier in patients with undervirilisation syndromes.
abstract: OBJECTIVE
  Fertility post-orchidopexy is dependent on transformation of neonatal gonocytes (G) into adult dark spermatogonia at about 3 months, the same time as gonadotrophins stimulate androgen secretion. We examined how androgen blockade affects transformation of gonocytes to spermatogonial stem cells (SSC) during this period in patients with undervirilisation syndromes.
  
  
  METHODS
  Patients with undervirilisation syndromes (n=30, 1.5 weeks-16 years) underwent review of medical records, pathology reports, and H&E slides of testes (ethics HREC32164). Fluorescent immunohistochemistry against anti-Mullerian hormone (AMH, Sertoli cells), mouse VASA homologue (MVH, germ cells) and DAPI (nuclei) allowed the number of MVH-positive gonocytes/spermatogonial stem cells per seminiferous tubular cross-section (G/T or SSC/T) to be counted.
  
  
  RESULTS
  Gonocytes (MVH-positive cells in the tubular lumen) were present in 15/16 patients under 2 years old. SSC (MVH-positive cells on the tubule basement membrane) were present in 25/30 patients. With increasing age, the mean number of SSC/T decreased from ~4 to 0, and G/T decreased from ~1.5 to 0. SSC were present in CAIS and PAIS patients at 1.5 and 3.5 weeks old, respectively.
  
  
  CONCLUSIONS
  Gonocytes transform into SSC earlier than expected in patients with undervirilisation syndromes. Lack of androgens may stimulate non-androgenic regulators to trigger transformation. Understanding how gonocytes transform may enable optimization of spermatogonial development to preserve fertility post-orchidopexy.
authors: Department of Paediatrics, University of Melbourne, VIC, 3010, Australia; FD Stephens Research Laboratory, Murdoch Children's Research Institute, Flemington Road, Parkville, VIC 3052, Australia.
authors: Shu
authors: S
authors: Su
authors: FD Stephens Research Laboratory, Murdoch Children's Research Institute, Flemington Road, Parkville, VIC 3052, Australia; Department of Anatomy and Neuroscience, University of Melbourne, Parkville, VIC 3052, Australia.
authors: Maciej
authors: M
authors: Szarek
authors: FD Stephens Research Laboratory, Murdoch Children's Research Institute, Flemington Road, Parkville, VIC 3052, Australia.
authors: Abigail
authors: A
authors: Vooght
authors: Department of Paediatrics, University of Melbourne, VIC, 3010, Australia; FD Stephens Research Laboratory, Murdoch Children's Research Institute, Flemington Road, Parkville, VIC 3052, Australia; Department of Urology, Royal Children's Hospital Melbourne, Flemington Road, Parkville, VIC 3052, Australia. Electronic address: john.hutson@rch.org.au.
authors: John
authors: J
authors: Hutson
authors: Department of Paediatrics, University of Melbourne, VIC, 3010, Australia; FD Stephens Research Laboratory, Murdoch Children's Research Institute, Flemington Road, Parkville, VIC 3052, Australia.
authors: Ruili
authors: R
authors: Li
mesh_terms: D000367:Age Factors; D001485:Basement Membrane / Q000473:pathology; D001706:Biopsy; D002454:Cell Differentiation / Q000502:physiology*; D012734:Disorders of Sex Development / Q000503:physiopathology*; D005854:Germ Cells / Q000473:pathology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010641:Phenotype; D012671:Seminiferous Tubules / Q000473:pathology; D012708:Sertoli Cells / Q000473:pathology; D013091:Spermatogenesis / Q000502:physiology*; D013093:Spermatogonia / Q000254:growth & development*
keywords: Androgen-insensitivity syndrome; Germ cells; Spermatogonia; Testes