Rapid Mitochondrial DNA Segregation in Primate Preimplantation Embryos Precedes Somatic and Germline Bottleneck

SummaryThe timing and mechanisms of mitochondrial DNA (mtDNA) segregation and transmission in mammals are poorly understood. Genetic bottleneck in female germ cells has been proposed as the main phenomenon responsible for rapid intergenerational segregation of heteroplasmic mtDNA. We demonstrate here that mtDNA segregation occurs during primate preimplantation embryogenesis resulting in partitioning of mtDNA variants between daughter blastomeres. A substantial shift toward homoplasmy occurred in fetuses and embryonic stem cells (ESCs) derived from these heteroplasmic embryos. We also observed a wide range of heteroplasmic mtDNA variants distributed in individual oocytes recovered from these fetuses. Thus, we present here evidence for a previously unknown mtDNA segregation and bottleneck during preimplantation embryo development, suggesting that return to the homoplasmic condition can occur during development of an individual organism from the zygote to birth, without a passage through the germline.

Graphical AbstractFigure optionsDownload as PowerPoint slideHighlights
► Rapid segregation of heteroplasmic mtDNA in blastomeres of preimplantation embryos
► Shift toward homoplasmy in offspring produced from heteroplasmic oocytes
► Heteroplasmic mtDNA maintained in oocytes recovered from these offspring
► Return to homoplasmy occurs during early development, without a germline passage