In mouse, the oocyte-to-embryo transition entails converting a highly differentiated oocyte to totipotent blastomeres. This transition is driven by degradation of maternal mRNAs, which results in loss of oocyte identity, and reprogramming of gene expression during the course of zygotic gene activation, which occurs primarily during the two-cell stage and confers blastomere totipotency. Full-grown oocytes are transcriptionally quiescent and mRNAs are remarkably stable in oocytes due to the RNA-binding protein MSY2, which stabilizes mRNAs, and low activity of the 5' and 3' RNA degradation machinery. Oocyte maturation initiates a transition from mRNA stability to instability due to phosphorylation of MSY2, which makes mRNAs more susceptible to the RNA degradation machinery, and recruitment of dormant maternal mRNAs that encode for critical components of the 5' and 3' RNA degradation machinery. Small RNAs (miRNA, siRNA, and piRNA) play little, if any, role in mRNA degradation that occurs during maturation. Many mRNAs are totally degraded but a substantial fraction is only partially degraded, their degradation completed by the end of the two-cell stage. Genome activation initiates during the one-cell stage, is promiscuous, low level, and genome wide (and includes both inter- and intragenic regions) and produces transcripts that are inefficiently spliced and polyadenylated. The major wave of genome activation in two-cell embryos involves expression of thousands of new genes. This unique pattern of gene expression is the product of maternal mRNAs recruited during maturation that encode for transcription factors and chromatin remodelers, as well as dramatic changes in chromatin structure due to incorporation of histone variants and modified histones.
- MeSH
- embryo savčí metabolismus MeSH
- genom MeSH
- myši MeSH
- oocyty metabolismus MeSH
- stabilita RNA genetika MeSH
- transkriptom genetika MeSH
- vývojová regulace genové exprese MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Research Support, N.I.H., Extramural MeSH
The introduction of different micromanipulation techniques into reproductive and developmental biology has helped us not only to answer many essential biological questions but it is now evident that these techniques also have wide practical applications. In human-assisted reproduction, the most commonly used approach is the injection of a donor sperm into the oocyte cytoplasm--intracytoplasmic sperm injection. It is, however, speculated that with these techniques it would be also possible to improve the oocyte developmental potential especially in those cases when the quality of the cytoplasm is rather poor and thus its function is compromised. Another important application would be the elimination of mutated mitochondrial DNA (mtDNA) by transferring the nuclear material from an abnormal oocyte into a healthy donor oocyte cytoplast. Some of these techniques were already successfully tested in experimental animals, but it is evident that before their introduction into human medicine many questions must be answered, and we must be sure that these approaches are absolutely or almost absolutely safe. In our contribution, we will be specifically oriented to the nuclear (nuclear material) replacement approaches that could be potentially used to prevent the transmission of mutated mtDNA from mother to offspring. Because these techniques are very delicate, some training with oocytes from other species other than human is strongly recommended. 2007, Elsevier Inc.
