title: Distribution of GFRA1-expressing spermatogonia in adult mouse testis.
abstract: In mice and other mammals, spermatogenesis is maintained by spermatogonial stem cells (SSCs), a cell population belonging to undifferentiated type A spermatogonia. In the accepted model of SSC self-renewal, Asingle (As) spermatogonia are the stem cells, whereas paired (Apaired (Apr)) and chained (Aaligned (Aal)) undifferentiated spermatogonia are committed to differentiation. This model has been recently challenged by evidence that As and chained (Apr and Aal), undifferentiated spermatogonia are heterogeneous in terms of gene expression and function. The expression profile of several markers, such as GFRA1 (the GDNF co-receptor), is heterogeneous among As, Apr and Aal spermatogonia. In this study, we have analysed and quantified the distribution of GFRA1-expressing cells within the different stages of the seminiferous epithelial cycle. We show that in all stages, GFRA1+ chained spermatogonia (Apr to Aal) are more numerous than GFRA1+ As spermatogonia. Numbers of chained GFRA1+ spermatogonia are sharply reduced in stages VII-VIII when Aal differentiate into A1 spermatogonia. GFRA1 expression is regulated by GDNF and in cultures of isolated seminiferous tubules, we found that GDNF expression and secretion by Sertoli cells is stage-dependent, being maximal in stages II-VI and decreasing thereafter. Using qRT-PCR analysis, we found that GDNF regulates the expression of genes such as Tex14, Sohlh1 and Kit (c-Kit) known to be involved in spermatogonial differentiation. Expression of Kit was upregulated by GDNF in a stage-specific manner. Our data indicate that GDNF, besides its crucial role in the self-renewal of stem cells also functions in the differentiation of chained undifferentiated spermatogonia.
authors.affiliation: Fondazione Pasteur Cenci Bolognetti, Section of Histology and Medical Embryology, Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, La Sapienza University of Rome, Via Antonio Scarpa 14, 00161 Rome, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Grasso
authors.forename: Andrea
authors.initials: A
authors.lastname: Fuso
authors.forename: Lisa
authors.initials: L
authors.lastname: Dovere
authors.forename: Dirk G
authors.initials: DG
authors.lastname: de Rooij
authors.forename: Mario
authors.initials: M
authors.lastname: Stefanini
authors.forename: Carla
authors.initials: C
authors.lastname: Boitani
authors.forename: Elena
authors.initials: E
authors.lastname: Vicini
mesh_terms: D000367:Age Factors; D000818:Animals; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism / Q000494:pharmacology; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000235:genetics / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D012670:Seminiferous Epithelium / Q000187:drug effects / Q000378:metabolism; D013093:Spermatogonia / Q000187:drug effects / Q000378:metabolism*; D013737:Testis / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: C494988:Gfra1 protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D051741:Kruppel-Like Transcription Factors; D000075722:Promyelocytic Leukemia Zinc Finger Protein; C513267:Zbtb16 protein, mouse