Document Detail

Mitochondrial DNA transmission, replication and inheritance: a journey from the gamete through the embryo and into offspring and embryonic stem cells.
MedLine Citation:
PMID:  20231166     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Mitochondrial DNA (mtDNA) encodes key proteins associated with the process of oxidative phosphorylation. Defects to mtDNA cause severe disease phenotypes that can affect offspring survival. The aim of this review is to identify how mtDNA is replicated as it transits from the fertilized oocyte into the preimplantation embryo, the fetus and offspring. Approaches for deriving offspring and embryonic stem cells (ESCs) are analysed to determine their potential application for the prevention and treatment of mtDNA disease.
METHODS: The scientific literature was investigated to determine how mtDNA is transmitted, replicated and segregated during pluripotency, differentiation and development. It was also probed to understand how the mtDNA nucleoid is regulated in somatic cells.
RESULTS: mtDNA replication is strictly down-regulated from the fertilized oocyte through the preimplantation embryo. At the blastocyst stage, the onset of mtDNA replication is specific to the trophectodermal cells. The inner cell mass cells restrict mtDNA replication until they receive the key signals to commit to specific cell types. However, it is necessary to determine whether somatic cells reprogrammed through somatic cell nuclear transfer, induced pluripotency or fusion to an ESC are able to regulate mtDNA replication so that they can be used for patient-specific cell therapies and to model disease.
CONCLUSIONS: Prevention of the transmission of mtDNA disease from one generation to the next is still restricted by our lack of understanding as to how to ensure that a donor karyoplast transferred to an enucleated oocyte is free of accompanying mutant mtDNA. Techniques still need to be developed if stem cells are to be used to treat mtDNA disease in those patients already suffering from the phenotype.
Justin C St John; Joao Facucho-Oliveira; Yan Jiang; Richard Kelly; Rana Salah
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review     Date:  2010-03-15
Journal Detail:
Title:  Human reproduction update     Volume:  16     ISSN:  1460-2369     ISO Abbreviation:  Hum. Reprod. Update     Publication Date:    2010 Sep-Oct
Date Detail:
Created Date:  2010-08-10     Completed Date:  2010-12-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9507614     Medline TA:  Hum Reprod Update     Country:  England    
Other Details:
Languages:  eng     Pagination:  488-509     Citation Subset:  IM    
Clinical Sciences Research Institute, Warwick Medical School, CSB-University Hospital, Coventry, UK.
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MeSH Terms
Blastocyst / cytology,  ultrastructure*
Cytoplasm / genetics,  ultrastructure
DNA Replication*
DNA, Mitochondrial / metabolism,  physiology*
Embryonic Stem Cells / cytology,  ultrastructure*
Germ Cells / cytology,  ultrastructure
Goats / genetics
Goldfish / genetics
Mitochondria / genetics
Sheep / genetics
Sus scrofa / genetics
Grant Support
//British Heart Foundation; //Medical Research Council
Reg. No./Substance:
0/DNA, Mitochondrial

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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