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 displayed by different germ cells suggesting different targets for the ligands. GDNF regulates cell fate decision of undifferentiated spermatogonia 'Science 287 (2000) 1489'. The role of NRTN was now approached by targeted overexpression in mouse testis. Between 3 and 5 weeks of age, transient degeneration of spermatogenic cells was observed in approximately 20% of all five transgenic lines generated. Spermatids and pachytene spermatocytes underwent segmental degeneration, if the rete testis was undilated. When it was dilated, the spermatids and spermatocytes were more generally depleted. After 5 weeks of age, spermatogenic defects were no more observed and the NRTN overexpressing mice were fertile. The data suggest that NRTN might regulate survival and differentiation of spermatocytes and spermatids, but the low penetrance indicates that either the transgene expression has not been high enough or NRTN is not as essential as GDNF for spermatogenesis.
Meng
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Institute of Biomedicine, Developmental Biology, Biomedicum Helsinki and HUCH-Diagnostics, PO Box 63 (Haartmaninkatu 8), FIN-00014 University of Helsinki, Helsinki, Finland.
Pata
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I
Pedrono
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E
Popsueva
A
A
de Rooij
D G
DG
Jänne
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M
Rauvala
H
H
Sariola
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H
D000818:Animals; D029721:Drosophila Proteins; D005786:Gene Expression Regulation; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D051101:Neurturin; D010641:Phenotype; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051096:Proto-Oncogene Proteins c-ret; D012333:RNA, Messenger / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D013091:Spermatogenesis / Q000187:drug effects* / Q000235:genetics; D013093:Spermatogonia / Q000166:cytology / Q000187:drug effects; D013737:Testis / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D029721:Drosophila Proteins; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; C495053:NRTN protein, human; D009414:Nerve Growth Factors; D051101:Neurturin; C495056:Nrtn protein, mouse; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila