title: Restoration of normal embryogenesis by mitochondrial supplementation in pig oocytes exhibiting mitochondrial DNA deficiency.
abstract: An increasing number of women fail to achieve pregnancy due to either failed fertilization or embryo arrest during preimplantation development. This often results from decreased oocyte quality. Indeed, reduced mitochondrial DNA copy number (mitochondrial DNA deficiency) may disrupt oocyte quality in some women. To overcome mitochondrial DNA deficiency, whilst maintaining genetic identity, we supplemented pig oocytes selected for mitochondrial DNA deficiency, reduced cytoplasmic maturation and lower developmental competence, with autologous populations of mitochondrial isolate at fertilization. Supplementation increased development to blastocyst, the final stage of preimplantation development, and promoted mitochondrial DNA replication prior to embryonic genome activation in mitochondrial DNA deficient oocytes but not in oocytes with normal levels of mitochondrial DNA. Blastocysts exhibited transcriptome profiles more closely resembling those of blastocysts from developmentally competent oocytes. Furthermore, mitochondrial supplementation reduced gene expression patterns associated with metabolic disorders that were identified in blastocysts from mitochondrial DNA deficient oocytes. These results demonstrate the importance of the oocyte's mitochondrial DNA investment in fertilization outcome and subsequent embryo development to mitochondrial DNA deficient oocytes.
authors.affiliation: Centre for Genetic Diseases, Hudson Institute of Medical Research, 27-31 Wright Street, Clayton, Vic 3168, Australia.|Department of Molecular and Translational Science, Monash University, 27-31 Wright Street, Clayton, Vic 3168, Australia.
authors.forename: Gael L M
authors.initials: GL
authors.lastname: Cagnone
authors.affiliation: Centre for Genetic Diseases, Hudson Institute of Medical Research, 27-31 Wright Street, Clayton, Vic 3168, Australia.|Department of Molecular and Translational Science, Monash University, 27-31 Wright Street, Clayton, Vic 3168, Australia.
authors.forename: Te-Sha
authors.initials: TS
authors.lastname: Tsai
authors.affiliation: Centre for Genetic Diseases, Hudson Institute of Medical Research, 27-31 Wright Street, Clayton, Vic 3168, Australia.|Department of Molecular and Translational Science, Monash University, 27-31 Wright Street, Clayton, Vic 3168, Australia.
authors.forename: Yogeshwar
authors.initials: Y
authors.lastname: Makanji
authors.affiliation: Centre for Genetic Diseases, Hudson Institute of Medical Research, 27-31 Wright Street, Clayton, Vic 3168, Australia.|Department of Molecular and Translational Science, Monash University, 27-31 Wright Street, Clayton, Vic 3168, Australia.
authors.forename: Pamela
authors.initials: P
authors.lastname: Matthews
authors.affiliation: Department of Molecular and Translational Science, Monash University, 27-31 Wright Street, Clayton, Vic 3168, Australia.|Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, 27-31 Wright Street, Clayton, Vic 3168, Australia.
authors.forename: Jodee
authors.initials: J
authors.lastname: Gould
authors.affiliation: Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA, 02115, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Bonkowski
authors.affiliation: Monash Micro Imaging, Monash University, 27-31 Wright Street, Vic 3168 Clayton, Australia.
authors.forename: Kirstin D
authors.initials: KD
authors.lastname: Elgass
authors.affiliation: School of Medical Sciences, University of New South Wales, NSW 2052, Australia.
authors.forename: Ashley S A
authors.initials: AS
authors.lastname: Wong
authors.affiliation: School of Medical Sciences, University of New South Wales, NSW 2052, Australia.
authors.forename: Lindsay E
authors.initials: LE
authors.lastname: Wu
authors.affiliation: Centre for Genetic Diseases, Hudson Institute of Medical Research, 27-31 Wright Street, Clayton, Vic 3168, Australia.|Department of Molecular and Translational Science, Monash University, 27-31 Wright Street, Clayton, Vic 3168, Australia.
authors.forename: Matthew
authors.initials: M
authors.lastname: McKenzie
authors.affiliation: Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA, 02115, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Sinclair
authors.affiliation: Centre for Genetic Diseases, Hudson Institute of Medical Research, 27-31 Wright Street, Clayton, Vic 3168, Australia.|Department of Molecular and Translational Science, Monash University, 27-31 Wright Street, Clayton, Vic 3168, Australia.
authors.forename: Justin C
authors.initials: JC
authors.lastname: St John
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000378:metabolism; D003470:Culture Media / Q000737:chemistry; D056915:DNA Copy Number Variations; D004272:DNA, Mitochondrial / Q000235:genetics*; D046149:Embryo Culture Techniques; D047108:Embryonic Development; D005260:Female; D005307:Fertilization in Vitro; D020869:Gene Expression Profiling; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism*; D011247:Pregnancy; D034421:Sus scrofa / Q000196:embryology / Q000235:genetics*; D013552:Swine
chemical_list: D003470:Culture Media; D004272:DNA, Mitochondrial