Essential role of the p110β subunit of phosphoinositide 3-OH kinase in male fertility

Elisa Ciraolo, Fulvio Morello, Robin M. Hobbs, Frieder Wolf, Romina Marone, Manuela Iezzi, Xiaoyun Lu, Giulio Mengozzi, Fiorella Altruda, Giovanni Sorba, Kaomei Guan, Pier Paolo Pandolfi, Matthias P. Wymann, Emilio Hirsch

Research output: Contribution to journalArticleResearchpeer-review

43 Citations (Scopus)

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 p110β develop testicular hypotrophy and impaired spermatogenesis, leading to a phenotype of oligo-azoospermia and defective fertility. The examination of testes from p110β-defective tubules demonstrates a widespread loss in spermatogenic cells, due to defective proliferation and survival of pre- and postmeiotic cells. In particular, p110βis 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 p110βinhibitor. These data establish that activation of the p110β PI3K isoform by c-Kit is required during spermatogenesis, thus opening the way to new treatments for c-Kit positive testicular cancers.

Original languageEnglish
Pages (from-to)704-711
Number of pages8
JournalMolecular Biology of the Cell
Volume21
Issue number5
DOIs
Publication statusPublished - 1 Mar 2010
Externally publishedYes

Cite this