Does supplementation of oocytes with additional mtDNA influence developmental outcome?
Stephen McIlfatrick,
Sean O’Leary,
Takashi Okada,
Alexander Penn,
Vy Hoang Thao Nguyen,
Lisa McKenny,
Shang-Yu Huang,
Eryk Andreas,
John Finnie,
Roy Kirkwood,
Justin C. St. John
Affiliations
Stephen McIlfatrick
Mitochondrial Genetics Group, School of Biomedicine, Faculty of Health and Medical Sciences, and Robinson Research Institute, The University of Adelaide, Adelaide Health and Medical Sciences Building, Adelaide, SA 5000, Australia
Sean O’Leary
Mitochondrial Genetics Group, School of Biomedicine, Faculty of Health and Medical Sciences, and Robinson Research Institute, The University of Adelaide, Adelaide Health and Medical Sciences Building, Adelaide, SA 5000, Australia
Takashi Okada
Mitochondrial Genetics Group, School of Biomedicine, Faculty of Health and Medical Sciences, and Robinson Research Institute, The University of Adelaide, Adelaide Health and Medical Sciences Building, Adelaide, SA 5000, Australia
Alexander Penn
Mitochondrial Genetics Group, School of Biomedicine, Faculty of Health and Medical Sciences, and Robinson Research Institute, The University of Adelaide, Adelaide Health and Medical Sciences Building, Adelaide, SA 5000, Australia
Vy Hoang Thao Nguyen
Mitochondrial Genetics Group, School of Biomedicine, Faculty of Health and Medical Sciences, and Robinson Research Institute, The University of Adelaide, Adelaide Health and Medical Sciences Building, Adelaide, SA 5000, Australia
Lisa McKenny
School of Animal and Veterinary Sciences, The University of Adelaide, Roseworthy Campus, Roseworthy, SA 5371, Australia
Shang-Yu Huang
Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital-Linkou Medical Center, Taoyuan, Taiwan; Chang Gung University, College of Medicine, Taoyuan, Taiwan
Eryk Andreas
Mitochondrial Genetics Group, School of Biomedicine, Faculty of Health and Medical Sciences, and Robinson Research Institute, The University of Adelaide, Adelaide Health and Medical Sciences Building, Adelaide, SA 5000, Australia
John Finnie
University Veterinarian & AWO, Office of the Deputy Vice-Chancellor (Research), The University of Adelaide, Adelaide Health and Medical Sciences Building, Adelaide, SA 5000, Australia
Roy Kirkwood
School of Animal and Veterinary Sciences, The University of Adelaide, Roseworthy Campus, Roseworthy, SA 5371, Australia
Justin C. St. John
Mitochondrial Genetics Group, School of Biomedicine, Faculty of Health and Medical Sciences, and Robinson Research Institute, The University of Adelaide, Adelaide Health and Medical Sciences Building, Adelaide, SA 5000, Australia; Corresponding author
Summary: Introducing extra mitochondrial DNA (mtDNA) into oocytes at fertilization can rescue poor quality oocytes. However, supplementation alters DNA methylation and gene expression profiles of preimplantation embryos. To determine if these alterations impacted offspring, we introduced mtDNA from failed-to-mature sister (autologous) or third party (heterologous) oocytes into mature oocytes and transferred zygotes into surrogates. Founders exhibited significantly greater daily weight gain (heterologous) and growth rates (heterologous and autologous) to controls. In weaners, cholesterol, bilirubin (heterologous and autologous), anion gap, and lymphocyte count (autologous) were elevated. In mature pigs, potassium (heterologous) and bicarbonate (autologous) were altered. mtDNA and imprinted gene analyses did not reveal aberrant profiles. Neither group exhibited gross anatomical, morphological, or histopathological differences that would lead to clinically significant lesions. Female founders were fertile and their offspring exhibited modified weight and height gain, biochemical, and hematological profiles. mtDNA supplementation induced minor differences that did not affect health and well-being.
