This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by St John, J. C Articles by El Shourbagy, S. Search for Related Content PubMed PubMed Citation Articles by St John, J. C Articles by El Shourbagy, S.

The consequences of nuclear transfer for mammalian foetal development and offspring survival. A mitochondrial DNA perspective

The Mitochondrial and Reproductive Genetics Group, The Division of Medical Sciences, The Medical School, The University of Birmingham, Birmingham B15 2TT, UK

Correspondence should be addressed to Justin C St John, Room EF20, The East Wing, The Medical School, The University of Birmingham, Birmingham B15 2TJ, UK; Email: j.stjohn{at}bham.ac.uk

The introduction of nuclear transfer (NT) and other technologies that involve embryo reconstruction require us to reinvestigate patterns of mitochondrial DNA (mtDNA) transmission, transcription and replication. MtDNA is a 16.6 kb genome located within each mitochondrion. The number of mitochondria and mtDNA copies per organelle is specific to each cell type. MtDNA is normally transmitted through the oocyte to the offspring. However, reconstructed oocytes often transmit both recipient oocyte mtDNA and mtDNA associated with the donor nucleus. We argue that the transmission of two populations of mtDNA may have implications for offspring survival as only one allele might be actively transcribed. This could result in the offspring phenotypically exhibiting mtDNA depletion-type syndromes. A similar occurrence could arise when nucleo–cytoplasmic interactions fail to regulate mtDNA transcription and replication, especially as the initiation of mtDNA replication post-implantation is a key developmental event. Furthermore, failure of the donor somatic nucleus to be reprogrammed could result in the early initiation of replication and the loss of cellular mtDNA specificity. We suggest investigations should be conducted to enhance our understanding of nucleo–cytoplasmic interactions in order to improve NT efficiency.

This article has been cited by other articles:

				A.L. Bredenoord, G. Pennings, and G. de Wert Ooplasmic and nuclear transfer to prevent mitochondrial DNA disorders: conceptual and normative issues Hum. Reprod. Update, September 4, 2008; (2008) dmn035v1. [Abstract] [Full Text] [PDF]

				R. Alberio, K. H Campbell, and A. D Johnson Reprogramming somatic cells into stem cells. Reproduction, November 1, 2006; 132(5): 709 - 720. [Abstract] [Full Text] [PDF]

				E.C. Spikings, J. Alderson, and J.C.St. John Transmission of mitochondrial DNA following assisted reproduction and nuclear transfer Hum. Reprod. Update, July 1, 2006; 12(4): 401 - 415. [Abstract] [Full Text] [PDF]

				R. E. Lloyd, J.-H. Lee, R. Alberio, E. J. Bowles, J. Ramalho-Santos, K. H. S. Campbell, and J. C. St. John Aberrant Nucleo-cytoplasmic Cross-Talk Results in Donor Cell mtDNA Persistence in Cloned Embryos Genetics, April 1, 2006; 172(4): 2515 - 2527. [Abstract] [Full Text] [PDF]

				S. H El Shourbagy, E. C Spikings, M. Freitas, and J. C St John Mitochondria directly influence fertilisation outcome in the pig Reproduction, February 1, 2006; 131(2): 233 - 245. [Abstract] [Full Text] [PDF]

				K. Takeda, M. Tasai, M. Iwamoto, A. Onishi, T. Tagami, K. Nirasawa, H. Hanada, and C. A. Pinkert Microinjection of Cytoplasm or Mitochondria Derived from Somatic Cells Affects Parthenogenetic Development of Murine Oocytes Biol Reprod, June 1, 2005; 72(6): 1397 - 1404. [Abstract] [Full Text] [PDF]