title: In vivo dynamics of GFRα1-positive spermatogonia stimulated by GDNF signals using a bead transplantation assay.
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.
authors.affiliation: Department of Veterinary Anatomy, The University of Tokyo, Yayoi, Tokyo, 113-8657, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Uchida
authors.affiliation: Department of Veterinary Anatomy, The University of Tokyo, Yayoi, Tokyo, 113-8657, Japan.
authors.forename: Kasane
authors.initials: K
authors.lastname: Kishi
authors.affiliation: Department of Veterinary Anatomy, The University of Tokyo, Yayoi, Tokyo, 113-8657, Japan.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Aiyama
authors.affiliation: Department of Veterinary Anatomy, The University of Tokyo, Yayoi, Tokyo, 113-8657, Japan.
authors.forename: Kento
authors.initials: K
authors.lastname: Miura
authors.affiliation: Department of Experimental Animal Model for Human Disease, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan.
authors.forename: Hinako M
authors.initials: HM
authors.lastname: Takase
authors.affiliation: Department of Experimental Animal Model for Human Disease, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Department of Experimental Animal Model for Human Disease, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Kanai-Azuma
authors.affiliation: Center of Biomedical Research, Kyusyu University, Fukuoka, 812-8582, Japan.
authors.forename: Tokuko
authors.initials: T
authors.lastname: Iwamori
authors.affiliation: Department of Veterinary Anatomy, The University of Tokyo, Yayoi, Tokyo, 113-8657, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Kurohmaru
authors.affiliation: Department of Veterinary Anatomy, The University of Tokyo, Yayoi, Tokyo, 113-8657, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Tsunekawa
authors.affiliation: Department of Veterinary Anatomy, The University of Tokyo, Yayoi, Tokyo, 113-8657, Japan. Electronic address: aykanai@mail.ecc.u-tokyo.ac.jp.
authors.forename: Yoshiakira
authors.initials: Y
authors.lastname: Kanai
mesh_terms: D000818:Animals; D002449:Cell Aggregation / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004343:Drug Implants / Q000008:administration & dosage; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000008:administration & dosage / Q000378:metabolism*; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D015398:Signal Transduction; D013091:Spermatogenesis / Q000187:drug effects / Q000502:physiology; D013093:Spermatogonia / Q000187:drug effects / Q000378:metabolism*; D055153:Stem Cell Niche / Q000187:drug effects; D013737:Testis / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D004343:Drug Implants; C495040:Gdnf protein, mouse; C494988:Gfra1 protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors
keywords: Bead transplantation; GDNF; Spermatogenesis; Spermatogonial stem cell; Testis