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Transmission of Dysfunctional Mitochondrial DNA and Its Implications for Mammalian Reproduction

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Cellular and Molecular Basis of Mitochondrial Inheritance

Part of the book series: Advances in Anatomy, Embryology and Cell Biology ((ADVSANAT,volume 231))

Abstract

Mitochondrial DNA (mtDNA) encodes proteins for the electron transport chain which produces the vast majority of cellular energy. MtDNA has its own replication and transcription machinery that relies on nuclear-encoded transcription and replication factors. MtDNA is inherited in a non-Mendelian fashion as maternal-only mtDNA is passed onto the next generation. Mutation to mtDNA can cause mitochondrial dysfunction, which affects energy production and tissue and organ function. In somatic cell nuclear transfer (SCNT), there is an issue with the mixing of two populations of mtDNA, namely from the donor cell and recipient oocyte. This review focuses on the transmission of mtDNA in SCNT embryos and offspring. The transmission of donor cell mtDNA can be prevented by depleting the donor cell of its mtDNA using mtDNA depletion agents prior to SCNT. As a result, SCNT embryos harbour oocyte-only mtDNA. Moreover, culturing SCNT embryos derived from mtDNA depleted cells in media supplemented with a nuclear reprograming agent can increase the levels of expression of genes related to embryo development when compared with non-depleted cell-derived embryos. Furthermore, we have reviewed how mitochondrial supplementation in oocytes can have beneficial effects for SCNT embryos by increasing mtDNA copy number and the levels of expression of genes involved in energy production and decreasing the levels of expression of genes involved in embryonic cell death. Notably, there are beneficial effects of mtDNA supplementation over the use of nuclear reprograming agents in terms of regulating gene expression in embryos. Taken together, manipulating mtDNA in donor cells and/or oocytes prior to SCNT could enhance embryo production efficiency.

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Acknowledgements

K.S. was supported by a Monash Graduate Scholarship and a Monash International Postgraduate Research Scholarship.

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Correspondence to Justin C. St. John .

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Srirattana, K., St. John, J.C. (2019). Transmission of Dysfunctional Mitochondrial DNA and Its Implications for Mammalian Reproduction. In: Sutovsky, P. (eds) Cellular and Molecular Basis of Mitochondrial Inheritance. Advances in Anatomy, Embryology and Cell Biology, vol 231. Springer, Cham. https://doi.org/10.1007/102_2018_3

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  • DOI: https://doi.org/10.1007/102_2018_3

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-04569-2

  • Online ISBN: 978-3-030-04570-8

  • eBook Packages: MedicineMedicine (R0)

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