In vivo dynamics of GFRα1-positive spermatogonia stimulated by GDNF signals using a bead transplantation assay

Biochem Biophys Res Commun. 2016 Aug 5;476(4):546-552. doi: 10.1016/j.bbrc.2016.05.160. Epub 2016 May 31.

Abstract

In mouse testes, spermatogonial stem cells (SSCs), a subpopulation of GFRα1 (GDNF family receptor-α1)-positive spermatogonia, are widely distributed along the convoluted seminiferous tubules. The proliferation and differentiation of the SSCs are regulated in part by local expression of GDNF (glial cell-derived neurotorphic factor), one of major niche factors for SSCs. However, the in vivo dynamics of the GDNF-stimulated GFRα1-positive spermatogonia remains unclear. Here, we developed a simple method for transplanting DiI-labeled and GDNF-soaked beads into the mouse testicular interstitium. By using this method, we examined the dynamics of GFRα1-positive spermatogonia in the tubular walls close to the transplanted GDNF-soaked beads. The bead-derived GDNF signals were able to induce the stratified aggregate formation of GFRα1-positive undifferentiated spermatogonia by day 3 post-transplantation. Each aggregate consisted of tightly compacted Asingle and marginal Apaired-Aaligned GFRα1-positive spermatogonia and was surrounded by Aaligned GFRα1-negative spermatogonia at more advanced stages. These data not only provide in vivo evidence for the inductive roles of GDNF in forming a rapid aggregation of GFRα1-positive spermatogonia but also indicate the usefulness of this in vivo assay system of various growth factors for the stem/progenitor spermatogonia in mammalian spermatogenesis.

Keywords: Bead transplantation; GDNF; Spermatogenesis; Spermatogonial stem cell; Testis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Aggregation / drug effects
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Drug Implants / administration & dosage
  • Glial Cell Line-Derived Neurotrophic Factor / administration & dosage
  • Glial Cell Line-Derived Neurotrophic Factor / metabolism*
  • Glial Cell Line-Derived Neurotrophic Factor Receptors / genetics
  • Glial Cell Line-Derived Neurotrophic Factor Receptors / metabolism*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Mice, Transgenic
  • Signal Transduction
  • Spermatogenesis / drug effects
  • Spermatogenesis / physiology
  • Spermatogonia / drug effects
  • Spermatogonia / metabolism*
  • Stem Cell Niche / drug effects
  • Testis / cytology
  • Testis / drug effects
  • Testis / metabolism

Substances

  • Drug Implants
  • Gdnf protein, mouse
  • Gfra1 protein, mouse
  • Glial Cell Line-Derived Neurotrophic Factor
  • Glial Cell Line-Derived Neurotrophic Factor Receptors