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

Sirtuin-mediated regulation of oocyte quality (#110)

Hayden Homer 1
  1. The University of Queensland, Herston, QLD, Australia

Oocytes contribute virtually all of the cytoplasmic building blocks and mitochondria required by the early embryo. Consequently, poor oocyte quality as occurs for instance during ageing, severely compromises pregnancy success. At present, the only effective means for countering poor oocyte quality in the clinic is to substitute better quality oocytes from younger donors, but at the expense of having offspring with a different genetic makeup. In spite of the growing challenge posed by poor oocyte quality, to-date there remains no clinically practicable means for rejuvenating oocytes. In large part, this stems from a limited understanding of the key players involved in determining oocyte quality at the molecular level. Prominent features of poor oocyte quality include increased chromosome segregation errors, impaired mitochondrial function and elevated oxidative stress. These are inter-dependent; for instance, reduced cellular energy compromises energy-demanding processes such as spindle assembly that in turn derails chromosome segregation fidelity. A crucially important unknown pertains to the identity of key upstream regulators in oocytes that might straddle all of these processes and might therefore be clinically tractable targets for modifying oocyte quality. In seeking to uncover key molecular regulators in oocytes, our work has led us to a seven-member family of NAD+-dependent deacetylases known as sirtuins (SIRT1-7). We find that inhibiting sirtuin activity is severely detrimental to oocyte maturation. Conversely, oocytes from genetically modified mice with enhanced sirtuin activity exhibit resilience to the ageing process. Sirtuin-centred pathways are therefore pivotal for oocyte quality and may be clinically relevant since sirtuin activity can potentially be modulated via oral agents that alter the levels of their essential co-factor, NAD+