title: Fibroblast growth factor receptor 3 is highly expressed in rarely dividing human type A spermatogonia.
abstract: Human spermatogonia (Spg) and their fetal precursors express fibroblast growth factor receptor 3 (FGFR3). To further elucidate the role of FGFR3 in the control of Spg self-renewal, proliferation, and/or differentiation, and to narrow down the FGFR3-positive cell type(s) in the normal adult human testis, tissue sections and whole mount preparations of seminiferous tubules were analyzed combining immunofluorescence and confocal fluorescence microscopy. FGFR3 protein was chiefly observed in cellular membranes and cytoplasmic vesicles of a subpopulation of type A Spg, which comprised the chromatin rarefaction zone-containing type A(dark). Cytoplasmic expression of FGFR3 and nuclear expression of proliferation-associated antigen KI-67 were mutually exclusive. Similarly, FGFR3-positive Spg were negative for Doublesex and Mab-3 related transcription factor 1 (DMRT1). By contrast, undifferentiated embryonic cell transcription factor 1 (UTF1) and survival time-associated PHD finger in ovarian cancer 1 protein (SPOC1) were co-expressed in the nuclei of FGFR3-positive Spg. Whole mounted seminiferous tubules illustrated the clonogenic arrangement of the FGFR3/UTF1 double-positive Spg, which mainly occurred as pairs or quadruplets and, different from the KIT-positive Spg, showed no overlap with KI-67 labeled clusters. Taken together, in the adult human testis, FGFR3 expression is a feature of small clones of rarely dividing type A Spg which resemble "undifferentiated" Spg, including the spermatogonial stem cells.
authors: Department of Andrology, University Hospital Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
authors: Kathrein
authors: K
authors: von Kopylow
authors: Hannah
authors: H
authors: Staege
authors: Wolfgang
authors: W
authors: Schulze
authors: Hans
authors: H
authors: Will
authors: Christiane
authors: C
authors: Kirchhoff
mesh_terms: D002455:Cell Division; D002462:Cell Membrane / Q000378:metabolism; D022162:Cytoplasmic Vesicles / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D005455:Fluorescent Antibody Technique; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008297:Male; D018613:Microscopy, Confocal; D009687:Nuclear Proteins / Q000096:biosynthesis; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000032:analysis / Q000096:biosynthesis*; D012671:Seminiferous Tubules / Q000166:cytology / Q000378:metabolism; D013091:Spermatogenesis / Q000502:physiology; D013093:Spermatogonia / Q000378:metabolism*; D013737:Testis / Q000166:cytology / Q000378:metabolism; D015534:Trans-Activators / Q000096:biosynthesis; D014157:Transcription Factors / Q000032:analysis / Q000096:biosynthesis
chemical_list: C110547:DMRT1 protein; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; C503048:PHF13 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C484738:UTF1 protein, human; C496365:FGFR3 protein, human; D019009:Proto-Oncogene Proteins c-kit; D051498:Receptor, Fibroblast Growth Factor, Type 3