Monkey Model for Mitochondrial Replacement by First Polar Body Transfer
A recent study published in Cell Research reported the first monkey model for mitochondrial replacement by first polar body transfer. The study was conducted by a team led by SUN Qiang and LIU Zhen at the Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology of the Chinese Academy of Sciences, CAS Key Laboratory of Primate Neuroscience.
Mitochondrion is a kind of organelle that carries part of DNA genetic material. Mutation of mitochondrial gene can lead to the occurrence of various diseases, and mitochondrial diseases are transmitted to offspring in the way of maternal inheritance. Mitochondrial replacement technology is currently the potential ideal treatment strategies of mitochondrial genetic diseases. One of the major problems faced before the clinical application of this technique is the efficacy and safety evaluation studies at the level of non-human primates which share similar germ cell characteristics with humans.
In this work, the team first conducted a detailed comparative analysis of the genomic integrity, epigenetic modification, DNA damage, and the number of mitochondrial DNA carried by the first pole between the cynomolgus monkey oocytes and the first polar body, demonstrating the potential feasibility of the first polar body to replace the nucleus of the oocyte. They then used micromanipulation to remove the nucleus of the recipient oocyte and transfer the first polar body of the donor oocyte to the reconstructed one of the recipient oocytes. The reconstructed oocytes were fertilized by ICSI so as to obtain the zygote with normal nucleus. After the zygote was transplanted, two cynomolgus monkeys of mitochondrial replacement mediated by first polar body transfer were obtained.
Genetic identification proved that these two monkeys were indeed obtained by first polar body replacement technology, and that the proportion of mitochondria from the first pole was less than 5% in the animals. This work is the first to demonstrate the effectiveness and safety of polar body replacement at the individual primate level, and has important reference significance for the treatment of mitochondrial genetic diseases and infertility caused by low ovarian reserve.
This work was mainly completed under the guidance of Researcher SUN Qiang and Researcher LIU Zhen. In addition, this work was supported by the cooperation of JING Naihe from the Center of Excellence in Molecular Cell Science of the Chinese Academy of Sciences. This work was supported by the Ministry of Science and Technology, National Natural Science Foundation of China and Shanghai Science and Technology Commission.