Date of Award

Spring 2007

Document Type

Dissertation - Restricted

Degree Name

Doctor of Philosophy (PhD)

Department

Biological Sciences

First Advisor

Waring, Gail

Second Advisor

Mynlieff, Michelle

Third Advisor

Yang, Pinfen

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 intraoocyte 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 hormoneinduced 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.

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