Mitochondrial function during mamalian oocyte development: going beyond bioenergetics

Adhikari D1, Liu J1, Alzubaidi U1, Zhang QH1, Yuen WS1, Robker RL2 and Carroll J1

  1. Department of Anatomy and Developmental Biology and Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia.
  2. The Robinson Research Institute, School of Medicine, The University of Adelaide, Australia 5005.

Due to limited glycolytic capabilities of mammalian oocytes, mitochondrial ATP production by OXPHOS is essential for oocyte and preimplantation embryo development. Mitochondrial biogenesis occurs throughout oocyte growth during which the number of mitochondria increases from about 1000 to up to 500,000. Mitochondrial DNA (mtDNA) amplifies and mitochondria undergo divisions during oocyte growth. mtDNA replication is driven by upregulation of Transcription Factor A, Mitochondrial (TFAM) and mitochondrial fission requires Dynamin-related Protein 1 (DRP1). Disruption of mitochondrial biogenesis by genetic ablation of TFAM or DRP1 during oocyte growth does not significantly reduce the levels of ATP in the fully grown oocyte. Furthermore, oocyte maturation, fertilization and early embryo development appear normal, although embryo development does not progress beyond day 15 of gestation. These findings suggest that the role of mitochondria in oocytes extends beyond that of a simple bioenergetics hub. Mitochondria are increasingly being recognized for coordinating multiple metabolic pathways and regulating nuclear modifications through metabolites. However, the roles of mitochondria in oocytes beyond ATP production are poorly understood. Primary or secondary mitochondrial defects in oocytes caused by maternal environment are known to be detrimental for embryo development and offspring health. Our analyses reveal altered metabolites, nuclear epigenetic modifications and nuclear gene expression profiles in TFAM and DRP1-deleted oocytes. Thus, the function of mitochondria in oocytes can be extended to include roles in regulating the levels of key metabolites that have potential to modify essential epigenetic modifications occurring during oocyte growth. In conclusion, our results show that oocyte mitochondria have roles that extend well beyond the traditional and widely held view that mitochondria act as a simple power supply for the purposes of maintaining oocyte function.