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Essential role of the p110beta subunit of phosphoinositide 3-OH kinase in male fertility

Ciraolo, Elisa and Morello, Fulvio and Hobbs, Robin M. and Wolf, Frieder and Marone, Romina and Iezzi, Manuela and Lu, Xiaoyun and Mengozzi, Giulio and Altruda, Fiorella and Sorba, Giovanni and Guan, Kaomei and Pandolfi, Pier Paolo and Wymann, Matthias P. and Hirsch, Emilio. (2010) Essential role of the p110beta subunit of phosphoinositide 3-OH kinase in male fertility. Molecular Biology of the Cell, 21 (5). pp. 704-711.

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Abstract

Phosphoinositide 3-kinases (PI3K) are key molecular players in male fertility. However, the specific roles of different p110 PI3K catalytic subunits within the spermatogenic lineage have not been characterized so far. Herein, we report that male mice expressing a catalytically inactive p110beta develop testicular hypotrophy and impaired spermatogenesis, leading to a phenotype of oligo-azoospermia and defective fertility. The examination of testes from p110beta-defective tubules demonstrates a widespread loss in spermatogenic cells, due to defective proliferation and survival of pre- and postmeiotic cells. In particular, p110beta is crucially needed in c-Kit-mediated spermatogonial expansion, as c-Kit-positive cells are lost in the adult testis and activation of Akt by SCF is blocked by a p110beta inhibitor. These data establish that activation of the p110beta PI3K isoform by c-Kit is required during spermatogenesis, thus opening the way to new treatments for c-Kit positive testicular cancers.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Biochemistry and Genetics > Cancer- and Immunobiology (Wymann)
UniBasel Contributors:Wymann, Matthias P.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Society for Cell Biology
ISSN:1059-1524
e-ISSN:1939-4586
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:08 Nov 2017 11:05
Deposited On:19 Jul 2013 07:35

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