Transient disruption of spermatogenesis by deregulated expression of neurturin in testis

Two related ligands, glial cell line-derived neurotrophic factor (GDNF) and neurturin (NRTN), are expressed by Sertoli cells, but their cognate ligand -binding co-receptors, GDNF family receptor alpha1 and alpha2, are displaye d by different germ cells suggesting different targets for the ligands. GDN F regulates cell fate decision of undifferentiated spermatogonia 'Science 2 87 (2000) 1489'. The role of NRTN was now approached by targeted overexpres sion in mouse testis. Between 3 and 5 weeks of age, transient degeneration of spermatogenic cells was observed in approximately 20% of all five transg enic lines generated. Spermatids and pachytene spermatocytes underwent segm ental degeneration, if the rete testis was undilated. When it was dilated, the spermatids and spermatocytes were more generally depleted. After 5 week s of age, spermatogenic defects were no more observed and the NRTN overexpr essing mice were fertile. The data suggest that NRTN might regulate surviva l and differentiation of spermatocytes and spermatids, but the low penetran ce indicates that either the transgene expression has not been high enough or NRTN is not as essential as GDNF for spermatogenesis, (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.