title: Variations in mouse mitochondrial DNA copy number from fertilization to birth are associated with oxidative stress.
abstract: Mitochondria are inherited maternally via the oocyte, which in the mouse contains 150-250 x 10(3) copies of mitochondrial DNA (mtDNA). The number of mtDNA copies/embryo is thought to be stable during cleavage, being progressively diluted/cell with each round of cell division, until replication begins at an undefined time post-implantation. Post-natally, tissues differ in copy number of mtDNA/cell, but when and how these differences arise is unclear. A ratiometric quantitative real-time polymerase chain reaction assay of the levels of a single mitochondrial gene against a single copy nuclear gene was used to estimate the average copy value of mtDNA/per cell from zygote to birth. A novel Bayesian statistical model was used to identify day 5.15-6.15 as the time at which replication recommences, consistent with the viability patterns of embryos carrying mitochondrial mutations. Mitochondrial DNA copy number/cell in a range of post-day 9.5 fetal and placental tissues showed tissue-specific temporal expression patterns. Western blotting was used to quantify post-day 9.5 tissue markers for oxidative stress and manganese superoxide dismutase, and revealed correlations with the changes in mtDNA copy number. These findings have potential implications for fetal programming, in-vitro embryo culture, and the mechanism underlying the mitochondrial bottleneck.
authors.affiliation: Department of Physiology, Development and Neuroscience, and Centre for Trophoblast Research, The Anatomy School, Downing Street, Cambridge CB2 3DY, UK.
authors.forename: Catherine Em
authors.initials: CE
authors.lastname: Aiken
authors.forename: Tereza
authors.initials: T
authors.lastname: Cindrova-Davies
authors.forename: Martin H
authors.initials: MH
authors.lastname: Johnson
mesh_terms: D000818:Animals; D001499:Bayes Theorem; D015153:Blotting, Western; D004247:DNA / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005306:Fertilization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D018384:Oxidative Stress; D011247:Pregnancy; D011270:Pregnancy, Animal; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D004247:DNA; D013482:Superoxide Dismutase