Poor correlations in the levels of pathogenic mitochondrial DNA mutations in polar bodies versus oocytes and blastomeres in humans

Am J Hum Genet. 2011 Apr 8;88(4):494-8. doi: 10.1016/j.ajhg.2011.03.010.


Because the mtDNA amount remains stable in the early embryo until uterine implantation, early human development is completely dependent on the mtDNA pool of the mature oocyte. Both quantitative and qualitative mtDNA defects therefore may negatively impact oocyte competence or early embryonic development. However, nothing is known about segregation of mutant and wild-type mtDNA molecules during human meiosis. To investigate this point, we compared the mutant levels in 51 first polar bodies (PBs) and their counterpart (oocytes, blastomeres, or whole embryos), at risk of having (1) the "MELAS" m.3243A>G mutation in MT-TL1 (n = 30), (2) the "MERRF" m.8344A>G mutation in MT-TK (n = 15), and (3) the m.9185T>G mutation located in MT-ATP6 (n = 6). Seven out of 51 of the PBs were mutation free and had homoplasmic wild-type counterparts. In the heteroplasmic PBs, measurement of the mutant load was a rough estimate of the counterpart mutation level (R(2) = 0.52), and high mutant-load differentials between the two populations were occasionally observed (ranging from -34% to +34%). The mutant-load differentials between the PB and its counterpart were higher in highly mutated PBs, suggestive of a selection process acting against highly mutated cells during gametogenesis or early embryonic development. Finally, individual discrepancies in mutant loads between PBs and their counterparts make PB-based preconception diagnosis unreliable for the prevention of mtDNA disorder transmission. Such differences were not observed in animal models, and they emphasize the need to conduct thorough studies on mtDNA segregation in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blastomeres / metabolism*
  • DNA, Mitochondrial / genetics*
  • DNA, Mitochondrial / metabolism*
  • Embryonic Development / genetics
  • Female
  • Humans
  • MELAS Syndrome / diagnosis
  • MELAS Syndrome / genetics
  • MELAS Syndrome / metabolism
  • MERRF Syndrome / diagnosis
  • MERRF Syndrome / genetics
  • MERRF Syndrome / metabolism
  • Male
  • Meiosis / genetics
  • Mutation*
  • Oocytes / metabolism*
  • Oogenesis / genetics
  • Pregnancy
  • Preimplantation Diagnosis


  • DNA, Mitochondrial