PTEN and primary ovarian failure: In our earlier study, we showed that constitutively enhanced oocyte PI3K–Akt signaling by loss of Pten (Phosphatase and tensin homolog) in primordial oocytes, which is the upstream negative regulator of PI3K–Akt signaling, causes global activation of all primordial follicles and premature ovarian failure (POF) [16].