TY - JOUR
T1 - Essential role of the p110β subunit of phosphoinositide 3-OH kinase in male fertility
AU - Ciraolo, Elisa
AU - Morello, Fulvio
AU - Hobbs, Robin M.
AU - Wolf, Frieder
AU - Marone, Romina
AU - Iezzi, Manuela
AU - Lu, Xiaoyun
AU - Mengozzi, Giulio
AU - Altruda, Fiorella
AU - Sorba, Giovanni
AU - Guan, Kaomei
AU - Pandolfi, Pier Paolo
AU - Wymann, Matthias P.
AU - Hirsch, Emilio
PY - 2010/3/1
Y1 - 2010/3/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77649101891&partnerID=8YFLogxK
U2 - 10.1091/mbc.E09-08-0744
DO - 10.1091/mbc.E09-08-0744
M3 - Article
SN - 1059-1524
VL - 21
SP - 704
EP - 711
JO - Molecular Biology of the Cell
JF - Molecular Biology of the Cell
IS - 5
ER -