Date of Award
Spring 2007
Document Type
Dissertation - Restricted
Degree Name
Doctor of Philosophy (PhD)
Department
Biological Sciences
First Advisor
Downs, Stephen M.
Second Advisor
Fitts, Robert H.
Third Advisor
Mynlieff, Michelle
Abstract
Soon after initiating meiosis, mammalian oocytes are arrested in the prophase I stage, which is equal to the G2/M transition. The meiotic-arrested state is maintained during the whole growing phase. Fully-grown and meiotically competent oocytes undergo meiotic resumption, or oocyte maturation, by the pre-ovulatory gonadotropin stimulation. However, the mechanism whereby meiotic maturation is controlled remains elusive. Meiotically competent oocytes maintained in meiotic arrest in vitro or in vivo can be stimulated to resume maturation by hormone action on the granulosa cells. Evidence shows that with hormonal stimulation, granulosa cells produce a positive signal, and then by a cell-cell coupling pathway regulate oocyte maturation. cAMP in the oocyte plays a critical role in maintaining oocyte meiotic arrest. A decrease of intra-oocyte cAMP concentration.is associated with meiotic resumption. 5'AMP, the byproduct of cAMP degradation, activates AMP-activated protein kinase (AMPK). Evidence has shown that AMPK protein is present in mouse oocytes and that AMPK activators can stimulate oocyte maturation in vitro. Our lab proposed that AMPK activation provides a positive stimulus to induce mouse oocyte meiotic resumption. My research work is focused on the role of AMPK in regulation of mouse oocyte meiotic resumption. The study is divided into four parts: (1) AMPK activation induces mouse oocyte meiotic resumption in vitro; (2) AMPK activity is involved in hormone-induced maturation in vitro and spontaneous maturation; (3) Pulsing ocytes with cAMP stimulates oocyte maturation through the activation of AMPK; (4) Examination of the roles of different AMPK isoforms in regulation of mouse oocyte maturation by using AMPK catalytic subunit knockout mice.