Impaired mitochondrial function in murine oocytes is associated with controlled ovarian hyperstimulationand in vitro maturation

Abstract

The present study was designed to determine whether controlled ovarian hyperstimulation (COH) and in vitro maturation (IVM), two common clinical procedures in human IVF treatment, have an impact on mitochondrial DNA (mtDNA) copy number and mitochondrial function in oocytes. Matured mouse oocytes recovered following COH, IVM and natural cycles (NC), which simulated those treatments in human clinic IVF treatment. The copies of mtDNA, the activity of mitochondria as determined by inner mitochondrial membrane potential and oocyte adenosine trisphosphate (ATP) content, pattern of mitochondrial distribution, reactive oxygen species (ROS) levels and the integrity of the cytoskeleton were evaluated in oocytes. Significant differences were detected between COH and NC groups in all measures, except the pattern of mitochondrial distribution and ROS levels. There were also significant differences detected between IVM and NC treatment groups in the copies of mitochondrial DNA, the level of ROS and the integrity of the cytoskeleton in oocytes. In conclusion, the results of this investigation indicate that non-physiological COH and IVM treatments inhibit mtDNA replication, alter mitochondrial function and increase the percentage of abnormal cytoskeleton and ROS production. Damage related to the mitochondria may partly explain the low efficiency of IVF and high rate of embryonic loss associated with these clinical procedures.