Ruili Li1, Damian Azzollini2, Ruidong Shen2, Jorgen Thorup3, Erick Clasen-Linde4, Dina Cortes5, John M Hutson6. 1. Douglas Stephens Surgical Research Group, Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Australia. Electronic address: ruili.li@mcri.edu.au. 2. Douglas Stephens Surgical Research Group, Murdoch Children's Research Institute, Melbourne, Australia. 3. Department of Paediatric Surgery, Rigshospitalet, Copenhagen, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. 4. Department of Pathology, Rigshospitalet, Copenhagen, Denmark. 5. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Pediatrics, Hvidovre University Hospital and University of Copenhagen, Denmark. 6. Douglas Stephens Surgical Research Group, Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Australia; Department of Urology, The Royal Children's Hospital, Melbourne, Australia.
Abstract
INTRODUCTION: Neonatal testicular germ cells/gonocytes, transform into stem cells for spermatogenesis during 'minipuberty', driving change in timing of surgery. This study examined gonocyte transformation in cryptorchid testes in children ≤18 months of age with unilateral, bilateral undescended testes (UDT), complete or partial androgen insensitivity syndrome (CAIS, PAIS) [3,4]. MATERIAL AND METHODS: Testicular biopsies were taken from patients with unilateral or bilateral UDT, PAIS or CAIS, aged 10 days-18 months. These testicular sections underwent immunohistochemistry with antibodies (Oct4, Ki67, C-Kit, Sox9) followed by confocal imaging, cell counting and statistical analysis. RESULTS: Both Sertoli cells/tubule and germ cells (GC)/tubule decreased with age, and % empty tubules (no GC) increased with age but with no significant differences between patient groups. Oct4+ germ cells/tubule decreased with age. There are some GCs and Sertoli cells proliferating during the first year and most proliferating Oct4+ germ cells (Oct4+/Ki67+) were located off tubular basement membrane. CONCLUSION: Our study showed that Oct4 expression gradually decreased after minipuberty and transformation into spermatogonia. Germ cells and Sertoli cells undergo mitosis during the first 12 months although not abundantly. We propose that Oct4+ gonocyte transformation into spermatogonia via proliferation and migration to the basement membrane may be delayed in UDT.
INTRODUCTION: Neonatal testicular germ cells/gonocytes, transform into stem cells for spermatogenesis during 'minipuberty', driving change in timing of surgery. This study examined gonocyte transformation in cryptorchid testes in children ≤18 months of age with unilateral, bilateral undescended testes (UDT), complete or partial androgen insensitivity syndrome (CAIS, PAIS) [3,4]. MATERIAL AND METHODS: Testicular biopsies were taken from patients with unilateral or bilateral UDT, PAIS or CAIS, aged 10 days-18 months. These testicular sections underwent immunohistochemistry with antibodies (Oct4, Ki67, C-Kit, Sox9) followed by confocal imaging, cell counting and statistical analysis. RESULTS: Both Sertoli cells/tubule and germ cells (GC)/tubule decreased with age, and % empty tubules (no GC) increased with age but with no significant differences between patient groups. Oct4+ germ cells/tubule decreased with age. There are some GCs and Sertoli cells proliferating during the first year and most proliferating Oct4+ germ cells (Oct4+/Ki67+) were located off tubular basement membrane. CONCLUSION: Our study showed that Oct4 expression gradually decreased after minipuberty and transformation into spermatogonia. Germ cells and Sertoli cells undergo mitosis during the first 12 months although not abundantly. We propose that Oct4+ gonocyte transformation into spermatogonia via proliferation and migration to the basement membrane may be delayed in UDT.