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Restoration of normal embryogenesis by mitochondrial supplementation in pig oocytes exhibiting mitochondrial DNA deficiency

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journal contribution
posted on 2024-06-18, 09:29 authored by GLM Cagnone, TS Tsai, Y Makanji, P Matthews, J Gould, MS Bonkowski, KD Elgass, ASA Wong, LE Wu, Matthew McKenzieMatthew McKenzie, DA Sinclair, JCS John
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.

History

Journal

Scientific Reports

Volume

6

Article number

ARTN 23229

Location

England

Open access

  • Yes

ISSN

2045-2322

eISSN

2045-2322

Language

English

Publication classification

C Journal article, C1.1 Refereed article in a scholarly journal

Copyright notice

2016, The Authors

Issue

1

Publisher

NATURE PORTFOLIO