Meiotic Purification of Dysfunctional Mitochondria in Mouse Oocytes

Mitochondrial purification during oogenesis is essential for the stable inheritance of the mitochondrial DNA. However, whether meiosis, the final stage of oogenesis, contributes to purification of dysfunctional mitochondria remains insufficiently demonstrated. Here, we observed that mitochondria within the first polar body (PB1) exhibit functional impairments compared to those retained in oocytes. TUNEL assays suggested that mitochondrial dysfunction in PB1 precedes the onset of nuclear genome apoptosis. In contrast, the second polar body (PB2) contains a mixture of both functional and dysfunctional mitochondria. By separately injecting dysfunctional mitochondria and functional mitochondria into germinal vesicle-stage mouse oocytes, we found that meiosis I actively direct dysfunctional mitochondria into PB1 while retain healthy mitochondria within the oocyte. Using PB1 and spindle transfer (PBT and ST) to introduce dysfunctional and functional mitochondria into meiosis II oocytes, respectively, we further found that meiosis II also expels dysfunctional mitochondria into PB2, while most functional mitochondria are retained in the oocyte. Only a small fraction of exogenous functional mitochondria was passively co-segregated into PB2 along with the nuclear genome in the ST group. Moreover, PB2 and pronuclear transfer (PB2T and PNT) experiments demonstrated that mitotic divisions lack the capacity to eliminate abnormal or foreign mitochondria. Together, these findings indicate that meiosis represents the final safeguard for mitochondrial quality control during oogenesis. Furthermore, it provides a mechanistic explanation for why mitochondrial donation at the second meiotic arrest stage (as in PB1T and ST) is more effective than at the fertilized egg stage (as in PB2T and PNT).