title: Mutation dependance of the mitochondrial DNA copy number in the first stages of human embryogenesis.
abstract: Mitochondrial DNA (mtDNA) content is thought to remain stable over the preimplantation period of human embryogenesis that is, therefore, suggested to be entirely dependent on ooplasm mtDNA capital. We have explored the impact of two disease-causing mutations [m.3243A>G myopathy, encephalopathy, lactic acidosis and stroke-like syndrome (MELAS) and m.8344A>G myoclonic epilepsy associated with ragged-red fibers (MERRF)] on mtDNA amounts in human oocytes and day 4-5 preimplantation embryos. The mtDNA amount was stable in MERRF and control materials, whereas gradually increasing from the germinal vesicle of oogenesis to the blastocyst stage of embryogenesis in MELAS cells, MELAS embryos carrying ∼3-fold higher mtDNA amount than control embryos (P = 0.0003). A correlation between mtDNA copy numbers and mutant loads was observed in MELAS embryos (R(2) = 0.42, P < 0.0013), suggestive of a compensation for the respiratory chain defect resulting from high mutation levels. These results suggest that mtDNA can replicate in early embryos and emphasize the need for sufficient amount of wild-type mtDNA to sustain embryonic development in humans.
authors: Institut Imagine and INSERM U781, Sorbonne Paris Cité, Hôpital Necker-Enfants Malades, Université Paris-Descartes, 149 rue de Sèvres, Paris cedex 15, France. sophie.monnot@inserm.fr
authors: Sophie
authors: S
authors: Monnot
authors: David C
authors: DC
authors: Samuels
authors: Laetitia
authors: L
authors: Hesters
authors: Nelly
authors: N
authors: Frydman
authors: Nadine
authors: N
authors: Gigarel
authors: Philippe
authors: P
authors: Burlet
authors: Violaine
authors: V
authors: Kerbrat
authors: Frédéric
authors: F
authors: Lamazou
authors: René
authors: R
authors: Frydman
authors: Alexandra
authors: A
authors: Benachi
authors: Josué
authors: J
authors: Feingold
authors: Agnes
authors: A
authors: Rotig
authors: Arnold
authors: A
authors: Munnich
authors: Jean-Paul
authors: JP
authors: Bonnefont
authors: Julie
authors: J
authors: Steffann
mesh_terms: D000140:Acidosis, Lactic / Q000235:genetics / Q000473:pathology; D056915:DNA Copy Number Variations; D004272:DNA, Mitochondrial / Q000235:genetics*; D047108:Embryonic Development / Q000235:genetics*; D006801:Humans; D017241:MELAS Syndrome / Q000235:genetics / Q000473:pathology; D017243:MERRF Syndrome / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D009865:Oocytes / Q000473:pathology; D009866:Oogenesis
chemical_list: D004272:DNA, Mitochondrial