The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2018

Mitochondrial distribution and trafficking is disrupted in oocytes from mitochondrial fission deficient and old mice (#30)

Jun Liu 1 , Deepak Adhikari 1 , Rebecca Robker 2 , John Carroll 1
  1. Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institue, Clayton, VIC, Australia
  2. The Robinson Research Institute, The University of Adelaide, North Adelaide, SA, Australia

Maternal ageing is associated with a dramatic decrease in fertility, which is primarily caused by an age-related decline in oocyte quality. Mitochondria are the most abundant organelle in the oocyte and play an important role in generating ATP during oocyte maturation. Importantly, during oocyte maturation, mitochondria undergo dramatic reorganisation that is dependent on motor protein dynein-mediated associations with microtubules, and surround the meiotic spindle. This study sought to determine whether the kinetics of mitochondrial re-localisation are disrupted in two different contexts of impaired mitochondrial function: i) oocytes that are deficient in fission due to null mutation in dynamin-related protein 1 (Drp1-/- mice) and ii) oocytes from aged females (1 year old mice).  Both mouse models were on the Dendra background so that all oocyte mitochondria were endogenously tagged with green fluorescence. Oocytes were collected at the germinal vesicle stage and induced to undergo maturation in vitro and imaged continuously by confocal microscopy.  Mitochondrial movements were monitored in real-time and re-localisation to the meiotic spindle was quantified. GV oocytes from both Drp1-/- mice and aged mice exhibited mitochondria that were clumped within the cytoplasm compared to homogeneously dispersed in young/wildtype mice. During maturation mitochondria in oocytes of young/ wildtype mice underwent rapid re-distribution and around 80% of mitochondria surrounded the meiotic spindle within 9h. Interestingly, oocyte mitochondria in Drp1-/- oocytes underwent spindle-associated aggregation with even greater efficiency than wildtype littermates. As these mitochondria are deficient in the fission machinery it suggests that enhanced mitochondrial connectivity results in more uniform relocalisation. In contrast, mitochondria in oocytes from old mice exhibited reduced trafficking to the developing meiotic spindle, with a greater proportion retained in the cytoplasm.  This indicates mitochondrial clusters in old oocytes are either deficient in dynein-mediated trafficking or more fragmented than mitochondria in oocytes of young females.