Poster Presentation The Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2014

Accumulation of electrophilic aldehydes during post-ovulatory ageing of mouse oocytes causes reduced fertility, oxidative stress and apoptosis (#322)

Tessa Lord 1 , Jacinta H Martin 1 , R John Aitken 1
  1. The University of Newcastle, CALLAGHAN, NSW, Australia

With increasing periods of time following ovulation, the mammalian MII stage oocyte experiences an overproduction of reactive oxygen species (ROS) and elevated levels of lipid peroxidation that are thought to be implicitly linked with functional deficiencies acquired during post-ovulatory ageing. Such deficiencies include a decline in fertilization rate, the production of poor quality embryos, and a heightened risk for abnormalities within offspring.

The current study has implicated electrophilic aldehydes produced as a consequence of lipid peroxidation as key mediators of post-ovulatory ageing and apoptosis in the murine MII oocyte. Immunocytochemistry identified the presence of electrophilic aldehydes such as 4-hydroxynonenal (4HNE) within the cell, whilst western blotting analyses depicted a covalent modification of oocyte proteins by 4HNE that was significantly elevated with extended periods of time post-ovulation (P<0.001). Time- and dose- dependent studies revealed that exposure to elevated levels of electrophilic aldehydes causes mitochondrial ROS production (P<0.001), lipid peroxidation (P<0.01), loss of mitochondrial membrane potential (P<0.001) and eventual apoptosis (P<0.01) within the oocyte. These intracellular changes are presumably a consequence of electron transport chain collapse, as the mitochondrial protein succinate dehydrogenase was identified as a primary target for covalent modification by 4HNE. Further to these findings, short-term exposure to physiological doses of 4HNE were found to dramatically impair the oocyte’s ability to participate in fertilization (P<0.01) and support embryonic development (P<0.001); however this loss of functionality could be restored by antioxidant supplementation (P<0.01). These data highlight the importance of timely fertilization of the mammalian oocyte post-ovulation and emphasize the need for supplementation of oocyte culture medium with antioxidant compounds when extended periods of culture prior to fertilization are unavoidable.