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1.  Role of Glial Cell Line–Derived Neurotrophic Factor in Germ-Line Stem Cell Fate 
The overall goal of this study is to unravel the role(s) played by glial cell line-derived neurotrophic factor (GDNF) in the fate of spermatogonial stem cells. There is great interest in the biology of spermatogonial stem cells, or Asingle spermatogonia, because of their importance in the treatment of infertility, the development of contraceptives, and the understanding of the etiology of testicular cancer, particularly seminoma. In the mouse, spermatogonial stem cells express GFRα-1, the receptor for GDNF, and respond to this growth factor in vivo and in vitro. GDNF is produced by the adjacent Sertoli cells, which are part of the germ-line stem cell niche in vertebrates. We specifically isolated GFRα-1–positive spermatogonia using an immunomagnetic bead technique. We then stimulated the cells with 100 ng/mL of rGDNF for 10 hours; unstimulated cells served as negative controls. Microarray analysis, immunocytochemistry, and Western blotting revealed that Numb, a regulator of the Notch pathway, is upregulated by GDNF in spermatogonial stem cells. There are indications that in rats, mice, and humans, the Notch pathway promotes spermatogonial differentiation. We observed that an increase in Numb expression is concomitant with Notch degradation in these cells. Thus, through Numb, GDNF might inhibit differentiation and allows the maintenance of the stem cell pool in the mouse seminiferous epithelium.
PMCID: PMC2904487  PMID: 16467260
GDNF; Notch; Numb; spermatogonia; testis stem cells
2.  ETV5 is required for continuous spermatogenesis in adult mice and may mediate blood–testes barrier function and testicular immune privilege 
The transcription factor Ets-variant gene 5 (ETV5) is essential for spermatogonial stem cell (SSC) self-renewal, as targeted deletion of the Etv5 gene in mice (Etv5−/−) results in only the first wave of spermatogenesis. Reciprocal transplants of neonatal germ cells from wild type and Etv5−/− testes were performed to determine the role of ETV5 in Sertoli cells and germ cells. ETV5 appears to be needed in both cell types for normal spermatogenesis. In addition, Etv5−/− recipients displayed increased interstitial inflammation and tubular involution after transplantation. Preliminary studies suggest that the blood-testis-barrier (Sertoli-Sertoli tight junctional complex) is abnormal in the Etv5−/− mouse.
PMCID: PMC2733827  PMID: 17911411
Ets-Related Molecule; ERM; Spermatogonial Stem Cell; Sertoli Cell; Germ Cell Transplantation

Results 1-2 (2)