Date of Award
Doctor of Philosophy
Aileen F. Keating
Metabolic perturbations including hyperinsulinemia that are induced during obesity and heat stress in humans and production animals are allied with several health hallmarks and impaired fertility. This dissertation research focused on charactering the impact of changes to central metabolism on ovarian function. We hypothesized that hyperinsulinemia induced during central metabolic perturbations, alters ovarian insulin-mediated PI3K signaling, negatively impacting ovarian folliculogenesis, steroidogenesis and xenobiotic biotransformation. To test this hypothesis, mRNA and protein expression profiles of insulin, PI3K, steroidogenic, inflammatory and chemical metabolism members were quantified using qRT-PCR, Western blotting or immunohistochemistry techniques using three models of hyperinsulinemia: 1) high fat diet (HFD)-induced obesity, 2) a transgenic mouse model of progressive obesity and 3) a porcine model of hyperinsulinemia. Overall, our data demonstrates that the ovarian insulin-KITLG-KIT-AKT signaling pathway is active and upregulated during central metabolic alterations. Perturbations to ovarian insulin-KITLG-KIT-AKT signaling pathway are likely to impact 1) follicle activation, oocyte viability and recruitment, 2) steroid hormone biosynthesis, and 3) xenobiotic biotransformation, potentially accelerating susceptibility to chemical exposure. All of these scenarios could lead to impairment of ovarian function, and may at least partially explain why female fecundity is compromised during altered metabolic states.
Nteeba, Jackson, "Impact of metabolic perturbation on ovarian function" (2014). Graduate Theses and Dissertations. 13675.