Concise reviews: Assisted reproductive technologies to prevent transmission of mitochondrial DNA disease.
Bottom Line: The available evidence indicates that cells removed from an eight-cell embryo are predictive of the mutation load in the entire embryo, indicating that PGD provides an effective risk reduction strategy for women who produce embryos with low mutation loads.For those who do not, research is now focused on meiotic nuclear transplantation techniques to uncouple the inheritance of nuclear and mtDNA.The scientific progress and associated regulatory issues are discussed.
Affiliation: Wellcome Trust Centre for Mitochondrial Research, Newcastle University, Newcastle upon Tyne, United Kingdom; Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.Show MeSH
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Mentions: Transplantation of the nuclear genome can be either performed on the fertilized egg, or before the oocyte is fertilized, for which the process of female meiosis offers several options (Fig. 1). Throughout its growth phase, the oocyte remains arrested in prophase of meiosis I with a very large nucleus known as the germinal vesicle (GV). The GV contains bivalent chromosomes formed during meiotic recombination when replicated maternal and paternal homologs become physically linked at sites of reciprocal exchange of DNA between nonsister chromatids to form crossovers, which in cytological studies are known as chiasmata 34. In the sexually mature female, a hormonal stimulus induces the fully grown oocytes to enter M phase of meiosis I. During the first meiotic division, crossovers are resolved and half of the resulting dyad chromosomes (each containing two chromatids) are expelled into the first polar body. This occurs shortly before the oocyte is ovulated. The dyad chromosomes remaining in the oocyte align on the meiosis II spindle and the oocyte remains arrested at this stage until sperm entry. This triggers the second meiotic division (MII) during which one chromatid of each chromosome is retained in the oocyte while the other is expelled into the second polar body. The haploid genomes from the oocyte and the sperm are then separately packaged into pronuclei (Fig. 1). Thus, in contrast to spermatogenesis, which produces four equal-sized gametes, female meiosis produces only one gamete capable of fertilization, the oocyte, which retains a haploid set of chromosomes and most of the cytoplasm.
Affiliation: Wellcome Trust Centre for Mitochondrial Research, Newcastle University, Newcastle upon Tyne, United Kingdom; Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.