Requirement of PI3Kbeta catalytic activity during spermatogenesis

Phosphoinositide 3-kinases (PI3K) play a crucial role in male fertility. However, the specific roles of different p110 PI3K catalytic subunits are currently unknown. Herein, we showed that mice engineered to express a catalytically inactive p110β present an impairment in spermatogenesis. Testes from mutant males were hypotrophic compared to those of wild-type controls and displayed the absence or strong reduction in the number of spermatogones and mature spermatozoa. This phenotype was not attributable to an impaired migration of primordial germ cells, since testes of five day old newborn males showed a regular number of Tra98-positive cells. Nonetheless, the seminiferous tubules of ten day old mutant mice showed a reduced proliferation and increased apoptosis of spermatogones. Thus, the absence of p110β catalytic activity phenocopied in vivo the genetic disruption of the PI3K binding site situated on the c-kit receptor. Indeed the in vitro treatment of wild-type spermatogones with a p110β-specific inhibitor blunted the kit ligand-induced phosphorylation of AKT. Overall, these findings establish p110β as crucial mediator of c-kit signaling in spermatogenesis.