(61) Mitochondrial Contribution to the Oocyte and Embryonic Development

Mitochondrial Contribution to the Oocyte and Embryonic Development

Grygarová Kateřina1,3,4; Miki Shavit1; and Nevoral Jan1,2

1. Biomedical Center,  Faculty of Medicine in Pilsen, Charles University, alej Svobody 76, 323 00 Pilsen, Czech Republic

2. Department of Histology and Embryology, Faculty of Medicine in Pilsen, Charles University, alej Svobody 76, 323 00 Pilsen, Czech Republic

3. Department of Histology and Embryology, Third Faculty of Medicine, Charles University, Ruská 87, 100 00 Prague 10, Czech Republic

4. Faculty of Science,  Charles University, Albertov 2038, 128 00 Nové Město, Prague, Czech Republic 

Abstract Text:

Mitochondria are traditionally recognized for their role in oxidative phosphorylation (OXPHOS) and energy production. However, in female reproduction, their significance extends beyond bioenergetics to biomolecule synthesis, epigenetic regulation, and mitochondrial (mt) genome storage. Notably, OXPHOS complex I is neither fully assembled nor active in the oocyte, and early embryonic development is characterized by very low metabolism and oxygen consumption. We hypothesized that mitochondrial depletion in oocytes does not compromise fertilization or early embryonic progression.We hypothesized that a diminished mitochondrial population does not compromise fertilization or early embryogenesis. To test this, we utilized a mouse model with a targeted depletion of mitochondria in oocytes, achieved through conditional knock-out of mitochondrial transcription factor A (Tfam) in oocytes (TfamloxPloxP/Zp3-Cre). Our results confirmed a significant reduction in mtDNA content in Tfamnull oocytes. Surprisingly, despite this depletion, fertilization rates and the early development of Tfam+/- embryos remained unaffected. Minimal TFAM expression from the parental allele was detected following embryonic genome activation, yet blastocysts successfully formed even with undetectable TFAM levels. Taken together, we suggest the dispensability of mitochondrial population in the oocyte and early embryonic development due to OXPHOS silence due to the late blastocyst. We expect the Warburg effect to cover the energy demand of the oocyte and early preimplantation embryo; on the other hand, while this metabolic adaptation may compensate for energy demands, the genetic implications of mitochondrial insufficiency warrant further investigation, particularly regarding potential mtDNA mutation accumulation and impaired biogenesis in later development.