Trans-generational maintenance of mitochondrial DNA integrity in oocytes during early folliculogenesis
We investigated the mtDNA dynamics during ovarian follicle development. Using base-editing, we generated mice harboring 3177 G>A mutation corresponding to the human Leber hereditary optic neuropathy related mtDNA mutation and confirmed the transgenerational decrease of mutant mtDNA. Using a mouse follicle culture system in which pathological mtDNA mutations were introduced in vitro followed by mtDNA sequencing and digital PCR, we found a decreased proportion of mutant mtDNA together with increased wild-type mtDNA during early folliculogenesis.