1. Long glucocorticoid-induced leucine zipper (L-GILZ) protein interacts with ras protein pathway and contributes to spermatogenesis control.
- Author
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Bruscoli S, Velardi E, Di Sante M, Bereshchenko O, Venanzi A, Coppo M, Berno V, Mameli MG, Colella R, Cavaliere A, and Riccardi C
- Subjects
- Animals, Extracellular Signal-Regulated MAP Kinases genetics, Extracellular Signal-Regulated MAP Kinases metabolism, Infertility, Male genetics, Infertility, Male metabolism, Male, Meiosis physiology, Mice, Mice, Knockout, Phosphorylation physiology, Protein Isoforms genetics, Protein Isoforms metabolism, Proto-Oncogene Proteins c-akt, Spermatogonia cytology, Transcription Factors genetics, ras Proteins genetics, Cell Differentiation physiology, Signal Transduction physiology, Spermatogenesis physiology, Spermatogonia metabolism, Transcription Factors metabolism, ras Proteins metabolism
- 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.
- Published
- 2012
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