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

Does exposure to ionising radiation damage mitochondria within oocytes? (#332)

Qiaochu Wang 1 , Jessica Stringer 1 , Karla Hutt 1 , John Carroll 1
  1. Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia

Anticancer treatments can damage oocytes and deplete the ovarian reserve, leading to premature ovarian failure and infertility. To devise new strategies to improve the long-term fertility and health of women post-treatment, it is necessary to understand the mechanisms by which treatments inflict this damage. Recent studies have largely focused on the ability of radiation therapy to damage oocyte nuclear DNA. However, the treatment may also damage intracellular organelles, such as mitochondria. We are investigating the hypothesis that radiation causes damage to mitochondria in oocytes, thereby contributing to depletion of the ovarian reserve and loss of oocyte quality. In this study, neonatal C57Bl6 female mice were untreated (controls) or subjected to whole body γ-irradiation (0.1Gy), and small (diameter≈20μm) and growing (diameter≈50μm) oocytes were collected 3 and 6 hours later. Staining with TMRM revealed a decrease in mitochondrial membrane potential in both small and growing oocytes after γ-irradiation, indicating that mitochondria were damaged. However, MitoTracker staining indicated that mitochondrial localization and abundance was not immediately affected by irradiation. Interestingly, mtDNA copy number was increased in growing oocytes after γ-irradiation compared to controls (p<0.05), which may be a compensatory mechanism to ensure the maintenance of mitochondrial function. When mice were superovulated more than 40 days after γ-irradiation, there was a significant reduction in the number of oocytes harvested compared to controls (0.1Gy 4±1/Control 18±1, n=16/6 mice, p<0.0001), though mitochondrial localization and membrane potential was similar between groups. As these irradiated mice are able to produce healthy pups, these preliminary/initial results indicate that oocytes that survive γ-irradiation and develop through to ovulation contain healthy mitochondria. Overall, if these studies indicate that anticancer treatment-induced mitochondrial damage contributes to depletion of the ovarian reserve or loss of oocyte quality, then protection of mitochondria may represent a novel strategy for alleviating anticancer treatments-mediated insult to the ovary.