Mitochondria in the egg are suggested to be crucial for the onset of new life. However, there is ambiguous knowledge about the necessity for fertilization and early embryonic development. Therefore, we created a conditional Tfam knockout (TfamloxP/loxP; Zp3-Cre) to produce Tfamnull oocytes for investigation of the mitochondrial abundance in oocytes and early embryos. This created mtDNA-depleted eggs, although the abundance of mitochondria did not change. Despite decreased mitochondrial membrane potential, Tfamnull oocytes matured and were fertilized, which led to embryo formation. These Tfamnull eggs were developed into mtDNA-deficient blastocysts. Both TFAM and mtDNA appear to be dispensable for the success of embryo implantation. Tfam expression and mtDNA replication rescue the mtDNA-deficient embryo after implantation, enabling passage through a post-implantation bottleneck, and allowing survivor embryos to develop into healthy individuals. Our findings highlight the uncoupled relationship between mtDNA replication and mitochondrial abundance in the growing oocyte and show the importance of the oocyte bulk mtDNA for successful mitochondrial activation in post-implantation embryos.

2nd Faculty of Medicine Department of Histology and Embryology Charles University Prague Czech Republic

3rd Faculty of Medicine Department of Histology and Embryology Charles University Prague Czech Republic

Faculty of Medicine in Pilsen Biomedical Center Charles University Prague Czech Republic

Faculty of Medicine in Pilsen Department of Histology and Embryology Charles University Pilsen Czech Republic

Faculty of Medicine in Pilsen Department of Pathological Physiology Charles University Pilsen Czech Republic

Faculty of Medicine in Pilsen Department of Physiology Charles University Pilsen Czech Republic

Faculty of Science University of South Bohemia České Budějovice Czech Republic

Institute of Parasitology Biology Centre Czech Academy of Sciences České Budějovice Czech Republic

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