Germline Selection by Meiosis Defends the Transmission of defective Mitochondria with mtDNA variants

SUMMARY Germline selection of mtDNA is vital in maternal inheritance of mtDNA, as it can eliminate severe mtDNA mutations. However, current evidence concerning germline selection at meiosis level comes from incomplete mtDNA sequencing in human first polar body (PB1), which lacks persuasion. Here, we found various variants, including pathogenic mutation sites, present on whole genome of mtDNA in human PB1 compared with its oocyte. And that PB1 mitochondria with mtDNA variants were defective. Afterwards, to further explore how mitochondria enter PB, the defective mitochondria transfer in mouse germline, including cumulus-oocyte-complexes at germinal vesicle and matured oocytes stage. It confirmed that in the first and second meiosis, active purification selected defective mitochondria into PB1 and PB2. Thus, twice meiosis is the last defense system for purifying selection of mtDNA mutations during oogenesis, which also demonstrated that PB1 and PB2 would be final destination of deleterious mtDNA mutations in germline selection.