Analysis of AMP-activated protein kinase (AMPK) in mouse oocyte meiotic maturation
Abstract
Oogenesis begins around the time of birth when oocytes enter into the first meiotic division and become arrested in the late stages of prophase (PI arrest). This arrest will last until the oocytes receive hormonal stimuli to complete the first division and enter the second cycle where they encounter the second meiotic arrest at metaphase II (MII arrest). The oocyte will be ovulated at this stage and complete meiosis only if fertilization occurs. The process between the prophase I arrest and metaphase II arrest is referred to as meiotic maturation or resumption of meiosis. The regulation of meiotic maturation is not well understood and remains an active area of research. It is firmly established that cAMP maintains the oocyte in meiotic arrest and that the reinitiation of meiosis is subsequent to a drop in oocyte cAMP levels. Phosphodiesterase (PDE) is an enzyme that hydrolyzes cAMP and has been shown to be indispensable for meiotic resumption. Our lab has explored the possibility that the end product of PDE action, 5'-AMP, activates the stress response kinase, AMP-activated protein kinase (AMPK). AMPK acts as a cellular fuel gauge of the cell and its activity is regulated by the AMP/ATP ratio. When a cell is exposed to stressful conditions, stimulation of AMPK turns off energy-consuming processes and turns on those that generate ATP. Our previous work has showed AMPK is present in mouse oocytes, and AICAR, a pharmacological activator of AMPK, stimulates GVB in meiotically-arrested oocytes. This study shows that exposing oocytes to a variety of stresses, including metabolic, oxidative, osmotic and heat, produces a significant induction of maturation. My research also shows that these stress treatments all result in the activation of the AMPK protein before GVB and using AMPK inhibitors, blocks stress-induced maturation. Taken as a whole, my study shows that oocytes exposed to stressful conditions are able to resume maturation through the activation of AMPK.
This paper has been withdrawn.