Date of Award
Spring 2002
Document Type
Dissertation - Restricted
Degree Name
Doctor of Philosophy (PhD)
Department
Biological Sciences
First Advisor
Downs, Stephen M.
Second Advisor
Hutz, Reinhold
Third Advisor
Piacsek, Bela
Abstract
Oogenesis is the process by which large precursor cells, primordial germ cells, differentiate into mature germ cells in the female. This process includes mitotic divisions to increase the number of precursor cells and meiosis to produce haploid gametes. Meiosis is arrested twice: once at prophase I and then again at metaphase II. In response to specific stimuli, the oocyte resumes meiosis and progresses to metaphase II; this process is termed oocyte maturation. The developmental mechanisms driving oocyte maturation are poorly understood. Previous work in our laboratory has shown that energy substrates such as glucose, glutamine and pyruvate can profoundly affect oocyte maturation. The role of glucose in oocyte maturation has been difficult to define, as it has to inhibit maturation, but is also necessary for hormone-induced maturation; the precise mechanisms driving this dual response of glucose are not known. The high circulating glucose level in patients with diabetes mellitus is known to be detriniental to · the development of the embryo. This study shows that meiotic maturation is compromised in oocytes from diabetic mice. Evidence suggests that the aberrations observed in the meiotic regulation may be the result of lack of hormone responsiveness. Metabolic pathways in the meiotic induction pathway have been shown to be compromised by the diabetic condition. An additional abnormality in the communication between the granulosa cells and the oocyte compartments has been detected. Through the activation of the polyol pathway in the oocytes, an accumulation of sorbitol may contribute to the irregularities observed in oocytes from diabetic mice. In this study, we show that the diabetic condition has detrimental effects on meiotic regulation in oocytes, thus possibly contributing to the developmental anomalies observed during embryo genesis.