Title : A pilot study investigating whether Mitoquinone (MitoQ) can reduce Reactive Oxygen Species (ROS)–induced mitochondrial dysfunction within human oocytes?
Abstract:
Today, women are more likely to pursue a career and bear children later in life if they wish to do so. Ageing alters oocyte quality due to Oxidative Stress (OS) on mitochondria. Resolving this could lead to an improved quality of life for a significant proportion of the population. The first aim of my study is the optimisation of MitoQ dosage or efficacy to mitigate ROS-induced mitochondrial dysfunction within human oocytes. The second objective is an evaluation of the safety of MitoQ. Human surplus oocytes obtained from IVF cycles would initially be cultured in TCM-199-based IVM mediums before being randomly assigned to control, ROS, and MitoQ groups. Oxidative stress would be induced using 50 µM H?O? before MitoQ treatment would be undertaken in increasing concentrations. MitoQ would be acquired from Antipodean Pharmaceutical Inc. Intracellular ROS, mitochondrial membrane potential, ATP production, mitochondrial morphology, follicle viability, and oocyte survival would each be assessed. ANOVA with dose–response analysis would be utilised to determine optimal MitoQ efficacy, and my research would comply with the Declaration of Helsinki, local ethical guidelines, and feedback from PPIE.
MitoQ treatment is expected to reduce intracellular ROS levels in a dose-dependent manner, whilst ATP levels and mitochondrial membrane potential should be maintained. Meanwhile, mitochondrial morphology should demonstrate reduced fragmentation and increased fusion, whilst improvements in follicular redox function and oocyte viability are also anticipated following MitoQ treatment. It is predicted that 1 µM MitoQ produces the greatest effect during this investigation. Previous studies have illustrated the evolutionary conservation and safety of MitoQ, thereby supporting progression to human phase 0 trials. The principal strengths of this pilot study include its use of human oocytes, dose-response design, and potential for future application. Equally, my research acknowledges limitations such as the small sample size and its in vitro nature. Potential confounding variables could be mitigated by regulating oocyte age and metabolic disorders, as well as excluding donors exposed to gonadotropins. Furthermore, the findings could provide a rationale for future in vivo studies which investigate fertilisation and embryonic development, with MitoQ showing immense promise for advancing in vitro maturation techniques.
