Human Reproduction Update Advance Access originally published online on March 31, 2006
Human Reproduction Update 2006 12(4):401-415; doi:10.1093/humupd/dml011
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Transmission of mitochondrial DNA following assisted reproduction and nuclear transfer
The Mitochondrial and Reproductive Genetics Group, The Medical School, University of Birmingham, Birmingham B15 2TT, UK
1 To whom correspondence should be addressed at: The Medical School, The University of Birmingham, Birmingham B15 2TT, UK. E-mail: j.stjohn.1{at}bham.ac.uk.
Submitted on November 25, 2005; accepted on February 28, 2006
Mitochondria are the organelles responsible for producing the majority of a cell’s ATP and also play an essential role in gamete maturation and embryo development. ATP production within the mitochondria is dependent on proteins encoded by both the nuclear and the mitochondrial genomes, therefore co-ordination between the two genomes is vital for cell survival. To assist with this co-ordination, cells normally contain only one type of mitochondrial DNA (mtDNA) termed homoplasmy. Occasionally, however, two or more types of mtDNA are present termed heteroplasmy. This can result from a combination of mutant and wild-type mtDNA molecules or from a combination of wild-type mtDNA variants. As heteroplasmy can result in mitochondrial disease, various mechanisms exist in the natural fertilization process to ensure the maternal-only transmission of mtDNA and the maintenance of homoplasmy in future generations. However, there is now an increasing use of invasive oocyte reconstruction protocols, which tend to bypass mechanisms for the maintenance of homoplasmy, potentially resulting in the transmission of either form of mtDNA heteroplasmy. Indeed, heteroplasmy caused by combinations of wild-type variants has been reported following cytoplasmic transfer (CT) in the human and following nuclear transfer (NT) in various animal species. Other techniques, such as germinal vesicle transfer and pronuclei transfer, have been proposed as methods of preventing transmission of mitochondrial diseases to future generations. However, resulting embryos and offspring may contain mtDNA heteroplasmy, which itself could result in mitochondrial disease. It is therefore essential that uniparental transmission of mtDNA is ensured before these techniques are used therapeutically.
Key words: assisted reproduction technology / mitochondrial DNA / nuclear transfer
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