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Concise reviews: Assisted reproductive technologies to prevent transmission of mitochondrial DNA disease.

Richardson J, Irving L, Hyslop LA, Choudhary M, Murdoch A, Turnbull DM, Herbert M - Stem Cells (2015)

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.

View Article: PubMed Central - PubMed

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.

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Related in: MedlinePlus

Schematic drawing showing progression from prophase of meiosis I (GV stage) to completion of meiosis II following fertilization. The diploid maternal genome contained in the large nucleus (GV) of the prophase I oocyte is packaged into bivalent chromosomes formed during meiotic recombination when pairs of replicated parental homologs become linked at the sites of reciprocal DNA exchange. Oocytes enter M phase of first meiotic division (MI) in response to hormonal stimulation and undergo anaphase of MI when bivalents are converted to dyad chromosomes, consisting of a pair of chromatids (at least one of which is a recombinant). Half of the dyads are ejected in the first polar body. The dyads remaining in the oocyte align on the second meiotic division (MII) spindle poised to undergo anaphase in response to sperm entry. During anaphase of MII dyads are resolved to single chromatids and half is lost in the second polar body. The chromatids remaining in the oocyte become surrounded by a nuclear membrane to form the female pronucleus. The products of the first and second meiotic divisions each contain a unique genome. Abbreviation: GV, germinal vesicle.
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fig01: Schematic drawing showing progression from prophase of meiosis I (GV stage) to completion of meiosis II following fertilization. The diploid maternal genome contained in the large nucleus (GV) of the prophase I oocyte is packaged into bivalent chromosomes formed during meiotic recombination when pairs of replicated parental homologs become linked at the sites of reciprocal DNA exchange. Oocytes enter M phase of first meiotic division (MI) in response to hormonal stimulation and undergo anaphase of MI when bivalents are converted to dyad chromosomes, consisting of a pair of chromatids (at least one of which is a recombinant). Half of the dyads are ejected in the first polar body. The dyads remaining in the oocyte align on the second meiotic division (MII) spindle poised to undergo anaphase in response to sperm entry. During anaphase of MII dyads are resolved to single chromatids and half is lost in the second polar body. The chromatids remaining in the oocyte become surrounded by a nuclear membrane to form the female pronucleus. The products of the first and second meiotic divisions each contain a unique genome. Abbreviation: GV, germinal vesicle.

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.


Concise reviews: Assisted reproductive technologies to prevent transmission of mitochondrial DNA disease.

Richardson J, Irving L, Hyslop LA, Choudhary M, Murdoch A, Turnbull DM, Herbert M - Stem Cells (2015)

Schematic drawing showing progression from prophase of meiosis I (GV stage) to completion of meiosis II following fertilization. The diploid maternal genome contained in the large nucleus (GV) of the prophase I oocyte is packaged into bivalent chromosomes formed during meiotic recombination when pairs of replicated parental homologs become linked at the sites of reciprocal DNA exchange. Oocytes enter M phase of first meiotic division (MI) in response to hormonal stimulation and undergo anaphase of MI when bivalents are converted to dyad chromosomes, consisting of a pair of chromatids (at least one of which is a recombinant). Half of the dyads are ejected in the first polar body. The dyads remaining in the oocyte align on the second meiotic division (MII) spindle poised to undergo anaphase in response to sperm entry. During anaphase of MII dyads are resolved to single chromatids and half is lost in the second polar body. The chromatids remaining in the oocyte become surrounded by a nuclear membrane to form the female pronucleus. The products of the first and second meiotic divisions each contain a unique genome. Abbreviation: GV, germinal vesicle.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4359624&req=5

fig01: Schematic drawing showing progression from prophase of meiosis I (GV stage) to completion of meiosis II following fertilization. The diploid maternal genome contained in the large nucleus (GV) of the prophase I oocyte is packaged into bivalent chromosomes formed during meiotic recombination when pairs of replicated parental homologs become linked at the sites of reciprocal DNA exchange. Oocytes enter M phase of first meiotic division (MI) in response to hormonal stimulation and undergo anaphase of MI when bivalents are converted to dyad chromosomes, consisting of a pair of chromatids (at least one of which is a recombinant). Half of the dyads are ejected in the first polar body. The dyads remaining in the oocyte align on the second meiotic division (MII) spindle poised to undergo anaphase in response to sperm entry. During anaphase of MII dyads are resolved to single chromatids and half is lost in the second polar body. The chromatids remaining in the oocyte become surrounded by a nuclear membrane to form the female pronucleus. The products of the first and second meiotic divisions each contain a unique genome. Abbreviation: GV, germinal vesicle.
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.

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.

View Article: PubMed Central - PubMed

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
Related in: MedlinePlus