The Phosphatidyl-inositol-3-kinase/AKT Pathway Controls mouse oocyte developmental competence

Molecular changes both within oocytes and with sur- rounding somatic cells contribute to oocyte maturation. Upon an ovulatory stimulus, follicular cells express EGF- like peptides that trigger the translation of specific mRNA transcripts during oocyte maturation, seemingly by indirect activation of the phosphatidyl-inositol-3-kinase cascade. We set out to explore the role of PI3K/AKT during oocyte matu- ration by using a genetic model where phosphatase and ten- sin homologue (Pten), which negatively regulates PI3K, is specifically ablated in oocytes. Western blots assessing AKT phosphorylation in Ptenfl/fl:ZP3-CRE oocytes revealed high levels of phosphorylation in GV stage oocytes and after 2.5h of culture with or without amphiregulin. Conversely, wild type oocytes showed transient phosphorylation of Akt only after 2.5h culture with amphiregulin. Translational activity measured by luciferase assay after intraoocyte injection of dual luciferase translation reporters showed translation that was no longer dependent on amphiregulin in Ptenfl/fl:ZP3- CRE oocytes. To assess developmental competence, we performed in vitro maturation and fertilization and found higher rates of fertilization when the PI3K/AKT/mTOR pathway was constitutively activated in the Ptenfl/fl:ZP3- CRE oocytes. These developmental rates were similar tothose obtained by incubating cumulus/oocyte complexes with amphiregulin. Given the anabolic role of the PI3K/AKT pathway and its possible effect on activation of key compo- nents controlling the meiotic cell cycle, we examined oocyte diameters and kinetics of meiotic resumption. No differences were found between Ptenfl/fl:ZP3-CRE and control oocytes, suggesting no effects on maturation rate. Collectively, our data show that the activation of the PI3K/AKT pathway pro- motes oocyte developmental competence by regulating the oocyte translational program.