Redox State and Ovarian Function
Infertility is recognized worldwide as a public health issue and there is a significant medical need to understand the mechanisms that underlie infertility so that we may progress towards designing better preventive and corrective measures. However, our current understanding of factors that impact fertility is not complete.
Oocyte quality is a major determinant of fertility, and the end quality of the oocyte is dependent upon proper execution of developmental events preceding its maturation and fertilization. Cellular redox state is suggested to modulate cell response and function and may be regulated during ovarian folliculogenesis. We hypothesize redox state is dynamic during ovarian folliculogenesis, and in part be controlled by follicle metabolism. Furthermore, we also hypothesize perturbations in normal physiological antioxidant capacity can negatively impact fertility.
This dissertation attempts to 1) spatially clarify the bioenergetics, metabolism, and the NADH/NAD+ redox couple in primordial through pre-ovulatory follicles in whole ovary using the Phasor Approach to Fluorescence lifetime imaging microscopy, 2) identify the contribution of glutathione (GSH) to proper maintenance of fertility, and 3) understand the effects of oxidative stress on the primordial follicle reserve, which is a major determinant of fertile lifespan.
Taken together, the work in this dissertation extends our understanding of bioenergetics, metabolism, and antioxidant requirements for normal folliculogenesis and proper oocyte quality.