Restoration of normal embryogenesis by mitochondrial supplementation in pig oocytes exhibiting mitochondrial DNA deficiency
| Autor: | Pamela Mary Matthews, David A. Sinclair, Ashley S.A. Wong, Justin C. St. John, Kirstin Elgass, Te-Sha Tsai, Yogeshwar Makanji, Matthew McKenzie, Michael Bonkowski, Jodee Gould, Gael Cagnone, Lindsay E. Wu |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Mitochondrial DNA DNA Copy Number Variations Swine Sus scrofa Embryonic Development Fertilization in Vitro Mitochondrion Biology DNA Mitochondrial Article Andrology Embryo Culture Techniques 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pregnancy medicine Animals Blastocyst Genetics 030219 obstetrics & reproductive medicine Multidisciplinary Gene Expression Profiling Embryo Oocyte Heteroplasmy Culture Media Mitochondria 030104 developmental biology medicine.anatomical_structure chemistry Oocytes Female DNA Mitochondrial DNA replication |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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