A team of researchers from the Newcastle University have developed a pioneering ‘three-person IVF’ technique, in which the fertilization procedure uses the nuclear DNA of the biological parents, and the mitochondrial DNA (mtDNA) from an oocyte donor. The technique, which facilitates exchange of DNA between two oocytes, could serve in preventing the transmission of mitochondrial diseases to offspring. The findings of the groundbreaking study have been published in the online edition of the journal, Nature.
The proof-of-principle study led by Mary Herbert and Professor Douglass M Turnbull from the North East England Stem Cell Institute, Newcastle University, UK, involved the extraction of pronuclei from the zygote of the biological parents, without removing the mtDNA. The researchers then used an oocyte donor’s fertilized egg and replaced its pronuclei with those extracted from the biological parents. The donor eggs used in this method contained 1 or 3 pronuclei, and were not suitable for IVF. With this, the genetic makeup comprised of DNA from the mother and father, and mtDNA from the donor. This technique was adopted to generate 80 zygotes, which were cultured for 6-7 days and monitored up to the development of the blastocyst stage. The study was carried out in accordance with the license provided by the Human Fertility and Embryology Authority (HFEA) in the year 2005.
The results showed that pronuclei could be transferred between abnormally fertilized zygotes with only minimal donor zygote mtDNA carry over. On optimizing the procedure, the average level of carry over was demonstrated to be <2% following two pronuclei transfers, with donor mtDNA not detectable in many embryos. The study thus suggests that the novel technique could be implemented to prevent the transmission of mitochondrial diseases.
Mitochondrial dysfunction is generally inherited from the maternal side (rarely from both parents), and may lead to a diverse range of common ailments such as hypertension, diabetes, osteoporosis, Alzheimer and Parkinson disease, multiple sclerosis, rheumatoid arthritis, and cancer. According to the fact sheet of the United Mitochondrial Disease Foundation (UMDF), mitochondrial DNA mutations occur in around 1 in 200 persons of the general population in the US, which may subsequently lead to disease development. UMDF further estimates that a child is born every 30 minutes, with the risk of developing mitochondrial disease by the age of 10 years.
Although currently, embryos are screened for maternal disease-associated mtDNA mutations with preimplantation genetic diagnosis, it is difficult to reliably predict the risk owing to the variability in the amount of healthy/abnormal mtDNA transferred to the embryos. With no known cure or treatment for mitochondrial diseases, research is ongoing to investigate or develop preventive and therapeutic strategies to combat the associated illnesses. The findings of the current study, which reveal the potential of the nuclear transfer technique in preventing mtDNA diseases, open a huge avenue for developing new, potentially life-saving technology.
1. Major breakthrough offers hope of preventing mitochondrial diseases. Press Release. Newcastle University. Last accessed April 20, 2010.
2. Craven L, Tuppen HA, Greggains GD, et al. Pronuclear transfer in human embryos to prevent transmission of mitochondrial DNA disease. Nature. 2010 May 6;465(7294):82-5.
3. Mitochondrial Disease Fact Sheet. United Mitochondrial Disease Foundation. Last accessed April 20, 2010.