Mitochondria in reproduction and fertility: mitochondria and embryo 2

Published on September 27, 2018   30 min

Other Talks in the Therapeutic Area: Gynaecology & Obstetrics

0:00
My name is Pascale May-Panloup. Currently, I am an Associate Professor and a hospital practitioner at the University Hospital of Angers, a city in the west of France. We will focus on mitochondria and embryo.
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Fertilization of the oocyte marks the beginning of embryonic development characterized by a succession of cell divisions before implantation and the appearance of the first cell differentiation. The first embryonic cell division takes place 11-20 hours after fertilization. At the first-cell stage, the embryonic genome is activated. At the 16-32 cell stage, cell contexts are established and blastomeres are compacted. The embryo is then called the morula. At the 80-200 cell stage, some recruits accumulate in the central cavity of the embryo under the action of Na+/K+ ATPase, leading to the formation of the blastocyte. The embryo then reaches the blastocyst stage. This period is accompanied large-scale synthesis of proteins. At this stage, the peripheral cells of the embryo differentiate in epithelial cell types to become the trophoectoderm, the internal mass forming the embryo itself. After leaving the zona pellucida, the trophoectoderm establishes contact with the myometrium endometrium allowing implantation of the embryo.
1:37
The variation of mtDNA content during embryogenesis was first evaluated in mouse embryo by Southern blot technique. So, these performing pulled embryos show that the mtDNA contents remain constant from the oocyte stage to around the time of implantation. These results were confirmed in mice by quantitative PC here. I refer to the dogma that there is no gate for the replication of mtDNA before implantation in rodents and before blastulation in large mammals. The phenomena contributing to this constancy seems more complex than originally envisaged. Once fertilization has taken place, a burst of mtDNA replication occurs just before embryonic genome activation. Ionic genome activation enacts the embryo to initiate the transcription of its own gene products, which means that this is no longer dependent on products carried over from the oocyte. The timing of embryonic genome activation is specific, generally occurring between the two and eight-cell stages. But, the mtDNA replication event is usually completed by the two-cells embryo stage. Sub-second mtDNA replication is restricted until the blastocyst stage. Even without a clear increase in mtDNA, this short replication event may blemish the mtDNA pool, answering that sufficient mtDNA is present to support embryo development. This has been shown in mouse and pig embryos. This figure shows the comparison of mtDNA content in both the oocytes and embryos at various stages of development. In the above model, we found no difference between metaphase two oocytes and two-cell embryos. This was followed by a significant decrease in mtDNA content between the two cells and the four/eight-cell stage. Then, the mtDNA content remained constant to the eight-cell stage and the morula stage, increasing dramatically at the blastocyst stage. The sudden sharp reduction of about 16 percent of the mtDNA content that we observed between the two-cells and the four/eight-cell stage is in favor of the active restriction of mtDNA rather than a reduced turnover of the molecules. A similar decrease of 98 percent between the two-cells and the eight-cell stage has also been evidenced in the peak. We may speculate that this active restriction also concerns the preparation of alternate maternal mitochondria. If it is true, the decrease of mtDNA content may constitute another bottleneck involving a reduction of mtDNA content followed by the drastic amplification of selected mitochondria, allowing the homogenization of mitochondrial genomes. Thus, the restriction amplification of mtDNA may hook you in multiple steps during oogenesis and embryogenesis is suggested by some authors.
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Mitochondria in reproduction and fertility: mitochondria and embryo 2

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