Mechanisms of oocyte lipid accumulation in obesity

Abstract

Metabolically altered environments have negative repercussions on the quality of cumulus oocyte complexes (COC). In obesity, the follicular fluid metabolic parameters are altered and lead to excessive lipid accumulation into COCs. However, it is still unknown the mechanisms by which this accumulation is stablished. Besides lipid accumulation, it is known that obesity decreases mitochondrial activity and induces endoplasmic reticulum stress on COCs. Until now, there are no studied determining in which moment and from which cell compartment these alterations are originated, neither what are the cellular repercussion in cumulus cells and immature and mature oocytes. The objectives of this project are to investigate the possible mechanism by which the oocyte accumulates lipids in obesity. The experiment 1 will aim to determine and compare lipid stocks in cumulus cell and oocytes in the final step of oocyte maturation in normal and obese mice. The experiment 2 will investigate four possible mechanism of lipid accumulation in cumulus cells and oocytes from pre-ovulatory follicles or ovulated oocytes from normal and obese mice. These four possible mechanisms are: (1) the increase in synthesis and storage of lipids into COCs; (2) the decrease of beta-oxidation; (3) the transport of fatty acids from cumulus cell to oocytes via fatty acid binding proteins (FABPs) and transzonal projections (TZPs); and (4) deficient lipophagy into COCs. Finally, if increased expression of FABPs in cumulus cell of obese mice were found, a third experiment will be conducted. The experiment 3 will aim to immunolocalize FABP into TZPs and determine the dynamics of FABP expression and lipid accumulation throughout the oocyte maturation in normal and obese mice. The results of the proposed project will allow to understand by which mechanisms the lipid accumulation occurs in oocytes, using the obesity as model. The results of this project will also reveal potential strategies that could be used to mitigate the negative effects of oocyte lipid accumulation on fertility.