Master of Science
Physiology and Pharmacology
Watson, Andrew J.
Betts, Dean H.
Obesity-induced hyperlipidemia is one of the main factors for female infertility. Hyperlipidemia, specifically with high levels of palmitic acid (PA) and oleic acid (OA), interferes with preimplantation development. Autophagy is essential in early embryo development but, it is unknown whether hyperlipidemia affects autophagic mechanisms in preimplantation embryos. It was hypothesized that PA will alter autophagy in preimplantation mouse embryos and that the subsequent effects will be reversed by OA. PA impaired blastocyst development by arresting embryos at the 8-cell stage. PA also elevated early embryo autophagy by increasing autophagosome formation, decreasing maturation, and disrupting degradation. Co-treatment with OA showed developmental delay at the early preimplantation stages but restored blastocyst formation. OA treatment also counteracted PA-induced effects on autophagy. Overall, PA altered autophagy at various levels, was reversed by the addition of OA. Ultimately, we aim to assist obese patients by offsetting the negative effects of hyperlipidemia on preimplantation embryo development.
Summary for Lay Audience
Obesity is a one of the main factors for infertility in Canadian females. Levels of fatty acids like palmitic acid (PA) and oleic acid (OA) are elevated in obese individuals. Previously, we reported that PA disrupts mouse embryonic development and addition of OA reversed those effects. Autophagy is another important mechanism in early embryo development in which useless contents are packaged into autophagosomes for degradation to be reused in other cellular functions. Despite the importance of autophagy in embryonic development, it is undefined whether autophagy is affected by elevated levels of fatty acids in preimplantation embryos. To determine the effects of PA and OA, mouse embryos were treated with PA and OA, alone and in combination for up to 48 hours. PA prevented embryonic development by arresting development at the 8-cell stage. PA also resulted in elevated levels of autophagy by disrupting autophagosome formation and lowering autophagosome maturation and degradation. OA addition to PA treatment resulted in developmental delay at the early embryonic stages but restored normal levels of development at the later stages. Additionally, PA and OA co-treatment reversed PA-effects on autophagic mechanisms of preimplantation mouse embryos. Overall, PA impaired development and elevated autophagy and the addition of OA counteracted those effects. With these findings, we expect to help obese individuals with their fertility problems by offsetting the negative effects of obesity on preimplantation embryo development.
Leung, Zuleika C. L., "Free fatty acid treatment alters autophagy during mouse preimplantation embryo development" (2021). Electronic Thesis and Dissertation Repository. 8160.
Available for download on Saturday, April 30, 2022