p19Ink4d and p18Ink4c cyclin-dependent kinase inhibitors in the male reproductive axis
Document Type
Journal ArticlePublication Date
2007-03-08Keywords
AnimalsCyclin-Dependent Kinase 4
Cyclin-Dependent Kinase 6
Cyclin-Dependent Kinase Inhibitor p18
Cyclin-Dependent Kinase Inhibitor p19
Gonadotrophs
Male
Mice
Mice, Knockout
Pituitary Gland, Anterior
Reproduction
Ribonucleoproteins
Testis
Cell Biology
Metadata
Show full item recordAbstract
The loss of the cyclin-dependent kinase inhibitors (CKIs) p18(Ink4c) and p19(Ink4d) leads to male reproductive defects (Franklin et al., 1998. Genes Dev 12: 2899-2911; Zindy et al., 2000. Mol Cell Biol 20: 372-378; Zindy et al., 2001. Mol Cell Biol 21: 3244-3255). In order to assess whether these inhibitors directly or indirectly affect male germ cell differentiation, we examined the expression of p18(Ink4c) and p19(Ink4d) in spermatogenic and supporting cells in the testis and in pituitary gonadotropes. Both p18(Ink4c) and p19(Ink4d) are most abundant in the testis after 18 days of age and are expressed in purified populations of spermatogenic and testicular somatic cells. Different p18(Ink4c) mRNAs are expressed in isolated spermatogenic and Leydig cells. Spermatogenic cells also express a novel p19(Ink4d) transcript that is distinct from the smaller transcript expressed in Sertoli cells, Leydig cells and in other tissues. Immunohistochemistry detected significant levels of p19(Ink4d) in preleptotene spermatocytes, pachytene spermatocytes, condensing spermatids, and Sertoli cells. Immunoprecipitation-Western analysis detected both CKI proteins in isolated pachytene spermatocytes and round spermatids. CDK4/6-CKI complexes were detected in germ cells by co-immunoprecipitation, although the composition differed by cell type. p19(Ink4d) was also identified in FSH+ gonadotrophs, suggesting that this CKI may be independently required in the pituitary. Possible cell autonomous and paracrine mechanisms for the spermatogenic defects in mice lacking p18(Ink4c) or p19(Ink4d) are supported by expression of these CKIs in spermatogenic cells and in somatic cells of the testis and pituitary.Source
Mol Reprod Dev. 2007 Aug;74(8):997-1007. Link to article on publisher's siteDOI
10.1002/mrd.20716Permanent Link to this Item
http://hdl.handle.net/20.500.14038/36052PubMed ID
17342741Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1002/mrd.20716
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