title: Cyclical and patch-like GDNF distribution along the basal surface of Sertoli cells in mouse and hamster testes.
abstract: OBJECTIVE
  In mammalian spermatogenesis, glial cell line-derived neurotrophic factor (GDNF) is one of the major Sertoli cell-derived factors which regulates the maintenance of undifferentiated spermatogonia including spermatogonial stem cells (SSCs) through GDNF family receptor α1 (GFRα1). It remains unclear as to when, where and how GDNF molecules are produced and exposed to the GFRα1-positive spermatogonia in vivo.
  
  
  RESULTS
  Here we show the cyclical and patch-like distribution of immunoreactive GDNF-positive signals and their close co-localization with a subpopulation of GFRα1-positive spermatogonia along the basal surface of Sertoli cells in mice and hamsters. Anti-GDNF section immunostaining revealed that GDNF-positive signals are mainly cytoplasmic and observed specifically in the Sertoli cells in a species-specific as well as a seminiferous cycle- and spermatogenic activity-dependent manner. In contrast to the ubiquitous GDNF signals in mouse testes, high levels of its signals were cyclically observed in hamster testes prior to spermiation. Whole-mount anti-GDNF staining of the seminiferous tubules successfully visualized the cyclical and patch-like extracellular distribution of GDNF-positive granular deposits along the basal surface of Sertoli cells in both species. Double-staining of GDNF and GFRα1 demonstrated the close co-localization of GDNF deposits and a subpopulation of GFRα1-positive spermatogonia. In both species, GFRα1-positive cells showed a slender bipolar shape as well as a tendency for increased cell numbers in the GDNF-enriched area, as compared with those in the GDNF-low/negative area of the seminiferous tubules.
  
  
  CONCLUSIONS
  Our data provide direct evidence of regionally defined patch-like GDNF-positive signal site in which GFRα1-positive spermatogonia possibly interact with GDNF in the basal compartment of the seminiferous tubules.
authors.affiliation: Department of Veterinary Anatomy, The University of Tokyo, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sato
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Aiyama
authors.forename: Mayuko
authors.initials: M
authors.lastname: Ishii-Inagaki
authors.forename: Kenshiro
authors.initials: K
authors.lastname: Hara
authors.forename: Naoki
authors.initials: N
authors.lastname: Tsunekawa
authors.forename: Kyoko
authors.initials: K
authors.lastname: Harikae
authors.forename: Mami
authors.initials: M
authors.lastname: Uemura-Kamata
authors.forename: Mai
authors.initials: M
authors.lastname: Shinomura
authors.forename: Xiao Bo
authors.initials: XB
authors.lastname: Zhu
authors.forename: Seishi
authors.initials: S
authors.lastname: Maeda
authors.forename: Sachi
authors.initials: S
authors.lastname: Kuwahara-Otani
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kudo
authors.forename: Hayato
authors.initials: H
authors.lastname: Kawakami
authors.forename: Masami
authors.initials: M
authors.lastname: Kanai-Azuma
authors.forename: Michio
authors.initials: M
authors.lastname: Fujiwara
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Miyamae
authors.forename: Shosei
authors.initials: S
authors.lastname: Yoshida
authors.forename: Makoto
authors.initials: M
authors.lastname: Seki
authors.forename: Masamichi
authors.initials: M
authors.lastname: Kurohmaru
authors.forename: Yoshiakira
authors.initials: Y
authors.lastname: Kanai
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D002452:Cell Count; D048430:Cell Shape; D006224:Cricetinae; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism*; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000378:metabolism; D008297:Male; D051379:Mice; D017440:Photoperiod; D021381:Protein Transport; D012671:Seminiferous Tubules / Q000166:cytology / Q000378:metabolism; D012708:Sertoli Cells / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D013093:Spermatogonia / Q000166:cytology / Q000378:metabolism; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology; D013696:Temperature; D013737:Testis / Q000166:cytology*
chemical_list: C494988:Gfra1 protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors