Mitochondrial DNA Supplementation of Oocytes Has Downstream Effects on the Transcriptional Profiles of Sus scrofa Adult Tissues with High mtDNA Copy Number

Oocytes can be supplemented with extra copies of mitochondrial DNA (mtDNA) to enhance developmental outcome. Pigs generated through supplementation with mtDNA derived from either sister (autologous) or third-party (heterologous) oocytes have been shown to exhibit only minor differences in growth, physiological and biochemical assessments, and health and well-being do not appear affected. However, it remains to be determined whether changes in gene expression identified during preimplantation development persisted and affected the gene expression of adult tissues indicative of high mtDNA copy number. It is also unknown if autologous and heterologous mtDNA supplementation resulted in different patterns of gene expression. Our transcriptome analyses revealed that genes involved in immune response and glyoxylate metabolism were commonly affected in brain, heart and liver tissues by mtDNA supplementation. The source of mtDNA influenced the expression of genes associated with oxidative phosphorylation (OXPHOS), suggesting a link between the use of third-party mtDNA and OXPHOS. We observed a significant difference in parental allelespecific imprinted gene expression in mtDNA-supplemented-derived pigs, with shifts to biallelic expression with no effect on expression levels. Overall, mtDNA supplementation influences the expression of genes in important biological processes in adult tissues. Consequently, it is important to determine the effect of these changes on animal development and health.Takashi Okada, Alexander Penn and Justin C. St. Joh