title: Long glucocorticoid-induced leucine zipper (L-GILZ) protein interacts with ras protein pathway and contributes to spermatogenesis control.
abstract: Correct function of spermatogonia is critical for the maintenance of spermatogenesis throughout life, but the cellular pathways regulating undifferentiated spermatogonia proliferation, differentiation, and survival are only partially known. We show here that long glucocorticoid-induced leucine zipper (L-GILZ) is highly expressed in spermatogonia and primary spermatocytes and controls spermatogenesis. Gilz deficiency in knock-out (gilz KO) mice leads to a complete loss of germ cell lineage within first cycles of spermatogenesis, resulting in male sterility. Spermatogenesis failure is intrinsic to germ cells and is associated with increased proliferation and aberrant differentiation of undifferentiated spermatogonia and with hyperactivity of Ras signaling pathway as indicated by an increase of ERK and Akt phosphorylation. Spermatogonia differentiation does not proceed beyond the prophase of the first meiotic division due to massive apoptosis associated with accumulation of unrepaired chromosomal damage. These results identify L-GILZ as a novel important factor for undifferentiated spermatogonia function and spermatogenesis.
authors: Department of Clinical and Experimental Medicine, Section of Pharmacology, Toxicology, and Chemotherapy, Medical School, University of Perugia, Via del Giochetto, 06122 Perugia, Italy.
authors: Stefano
authors: S
authors: Bruscoli
authors: Enrico
authors: E
authors: Velardi
authors: Moises
authors: M
authors: Di Sante
authors: Oxana
authors: O
authors: Bereshchenko
authors: Alessandra
authors: A
authors: Venanzi
authors: Maddalena
authors: M
authors: Coppo
authors: Valeria
authors: V
authors: Berno
authors: Maria Grazia
authors: MG
authors: Mameli
authors: Renato
authors: R
authors: Colella
authors: Antonio
authors: A
authors: Cavaliere
authors: Carlo
authors: C
authors: Riccardi
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D007248:Infertility, Male / Q000235:genetics / Q000378:metabolism; D008297:Male; D008540:Meiosis / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation / Q000502:physiology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction / Q000502:physiology*; D013091:Spermatogenesis / Q000502:physiology*; D013093:Spermatogonia / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C498608:Dsip1 protein, mouse; D020033:Protein Isoforms; D014157:Transcription Factors; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D018631:ras Proteins