Long Glucocorticoid-induced Leucine Zipper (L-GILZ) è essenziale per il controllo della spermatogenesi

A correct balance between spermatogonial stem cells (SSCs) self-renewal and differentiation is essential for the maintenance of spermatogenesis, but the cellular pathways regulating proliferation, differentiation and survival of the undifferentiated spermatogonia are partially known.Glucocorticoid-Induced Leucine Zipper (GILZ), is a mediator of the anti-inflammatory and immunomodulatory effects of glucocorticoids because GILZ controls the cell proliferation and differentiation. L-GILZ, the longer isoform of GILZ, is the only isoform expressed in spermatogonia and primary spermatocytes. The aim of this project is to understand the role of L-GILZ in the control of spermatogenesis.In this work I show that L-GILZ is an essential mediator of the spermatogenesis. Indeed,gilzdeficiency in knock-out mice leads to a complete loss of germ cell lineage within first cycles of spermatogenesis, resulting in male sterility with a phenotype similar to pathological features of Sertoli Cell-Only Syndrome. Spermatogenesis failure is intrinsic to germ cells and is associated with increased proliferation and aberrant differentiation of undifferentiated spermatogonia, with hyperactivity of Ras signaling pathway, and with a massive apoptosis during meiotic phase.This discovery is a clear advance in our knowledge of the mechanisms underlying spermatogenesis and indicate L-GILZ as a possible marker for diagnosis and a target for novel therapies to intervene in male sterility.