Date of Award
Doctor of Philosophy (PhD)
Stephen M. Downs
Mammalian oogenesis begins during fetal development. Oocytes enter meiosis and arrest at prophase I before birth. Meiosis resumes after proper hormonal signaling, the oocyte completes meiosis I, and then ovulates in metaphase II, at which stage it arrests until fertilization occurs. Egg activation occurs upon sperm fertilization, which includes various physiological processes including calcium influx, release of cortical granules, and completion of meiosis II. However, egg activation can also occur without fertilization, which compromises the later embryonic development. The developmental period from prophase I to metaphase II is referred as oocyte maturation, and involves crucial dynamic change of the cytoskeleton network. The underlying mechanisms that control meiotic regulation still remain elusive. It is well established that a high cAMP level is required to maintain prophase I arrest, whereas mitogen activated protein kinase (MAPK) activity is needed for later metaphase II arrest of the oocyte. cAMP declines during meiotic resumption by the activation of phosphodiesterase (PDE), which converts cAMP into AMP. Elevated AMP activates AMP-activated protein kinase (AMPK). It was suggested that activation of AMPK provides an additional stimulus for meiotic resumption, and consistent with this idea, activation of AMPK mediates meiotic resumption both in vivo and in vitro. However, the role of AMPK in later process remained to be determined.
My research is focused on the role of AMPK after meiotic resumption. It is composed of three parts: (1) the effect of AMPK activation on completion of oocyte maturation; (2) the regulation of AMPK activity by spindle microtubules; and (3) AMPK regulation of egg activation. Results indicate that AMPK promotes anaphase onset and formation of the first polar body (PB). Meanwhile, the activity and localization of AMPK is dependent on spindle microtubule integrity. In addition, AMPK suppresses premature activation of oocytes by maintaining MAPK activity.