Poster Presentation Annual Meetings of the Endocrine Society of Australia and Society for Reproductive Biology and Australia and New Zealand Bone and Mineral Society 2016

Lipid peroxidation contributes to the ROS mediated deterioration of meiotic competency and quality of oocytes (#441)

Bettina P Mihalas 1 , Nicole J Camlin 1 , Eileen A Mclaughlin 1 2 , Brett Nixon 1
  1. University of Newcastle, Callaghan, NSW, Australia
  2. Biological Sciences, The University of Auckland, Auckland, New Zealand

Oocytes remain arrested at prophase I (GV) from birth until meiotic resumption, which in humans can occur decades later. As such, they are susceptible to accumulative damage as women age. There is significant clinical evidence to suggest the accumulation of reactive oxygen species (ROS) in the ovary correlates with increased maternal age, reduced oocyte quality, diminished embryo development and a reduction in live births. Despite this, the mechanism(s) by which ROS elicit damage to GV oocytes remain largely unexplored. We propose that ROS mediated lipid peroxidation is a major contributor to the age-related decline in oocyte quality. In support of this hypothesis, we have established that oocytes from reproductively aged mice (14 months) carry a higher oxidative burden, including elevated ROS and expression of the lipid peroxidation product, 4-hydroxynonenal (4HNE), than oocytes from young mice (4-6 weeks). To explore the biological implications of this oxidative burden we have subjected GV oocytes from young mice to H2O2 and/or 4HNE prior to in vitro maturation (IVM). Following exposure to H2O2, GV oocytes experienced a dose-dependent elevation of 4HNE and this reactive aldehyde remained at high levels in metaphase II (MII) arrested oocytes. Additionally, both H2O2 and 4HNE exposure at GV arrest resulted in a decrease in meiotic completion during IVM. Those oocytes able to reach MII were characterised by significantly higher rates of spindle abnormalities and chromosome misalignments. H2O2 treated oocytes also exhibited proportionally larger MII spindles. In terms of its localisation, 4HNE was found to accumulate in the vicinity of MI and MII spindles in untreated eggs, but formed distinctive aggregates around the severely disrupted MI and MII spindles after H2O2 treatment. This observation suggests that elevated levels of ROS can disrupt spindle assembly and thus provide novel insight into causative factors that may contribute to age-related decline in oocyte quality.