The role of Akt signalling in the mammalian ovary

Abstract

The serine/threonine protein kinase Akt is involved in many cellular processes including cell growth, survival, proliferation and metabolism. Akt activity is modulated downstream of phosphatidylinositol-3-kinase (PI3K) in response to different extracellular stimuli. In the mammalian ovary, Akt collaborates with other kinases in the regulation of coordinate follicle and oocyte development. Akt determines the pool of primordial follicles and the transition from quiescent to growing phase. In addition, the kinase modulates granulosa cell apoptosis throughout folliculogenesis. In oocytes Akt participates in the control of meiosis resumption and, at metaphase II stage, regulates polar body emission and spindle organization. Its inhibition negatively affects preimplantation embryo development. As a consequence of such a central role, Akt dysregulation is associated with several human diseases including infertility and ovarian cancer.

Sex-Specific Regulation of AMP-Activated Protein Kinase (AMPK) in the Pacific Oyster Crassostrea gigas1

“…In C. gigas females at stage 3, compared with males and other stages, a significant increase of AKT mRNA levels was demonstrated. This observation supports the hypothesis that glucose metabolism is involved in vitellogenesis and/or in the late maturation stage in oyster, as demonstrated in vertebrates and fishes [114,115].…”

Deregulation of key signaling pathways involved in oocyte maturation in FMR1 premutation carriers with Fragile X-associated primary ovarian insufficiency

“…3). These results are in consonance with the deregulation of the PI3K/AKT pathway found in FXPOI females, as it is well known that this pathway can regulate many aspects of cell function (Cecconi et al, 2012). In this scenario, Lu et al (2012) found an increased apoptosis of follicle cells and an alteration of the AKT signaling cascade in ovaries of the FMR1 knock-in model.…”

“…1). Several lines of evidence have indicated that the PI3K/AKT gene family is critical regulator of follicle growth, differentiation and survival (Cecconi et al, 2012). In fact, lack of basal level of PI3K activation leads to the premature depletion of the pool of primordial follicles and to the development of POI (Reddy et al, 2009).…”

Repeated ovarian stimulation does not affect the expression level of proteins involved in cell cycle control in mouse ovaries and fallopian tubes

“…This conclusion has been further confirmed by the similar levels of β-catenin and by the absence of pAKT and p53 in FT of control and hyperstimulated groups. In humans, the abnormal activation of the PI3K/AKT pathway [34] and increased nuclear β-catenin levels have been described to occur in OC [35]. Also in mice, high-grade serous OC can arise from the FT following deletion of PTEN, a negative regulator of PI3K pathway [36].…”