Early embryonic development is characterized by a plethora of very complex and simultaneously operating processes, which are constantly changing cellular morphology and behaviour. After fertilization, blastomeres of the newly created embryo undergo global epigenetic changes and simultaneously initiate transcription from the zygotic genome and differentiation forming separate cell lineages. Some of these mechanisms were extensively studied during the last several decades and valuable insight was gained into how these processes are regulated at the molecular level. We have, however, a still very limited understanding of how multiple events are coordinated during rapid development of an early mammalian embryo. In this review, we discuss some aspects of early embryonic development in mammals, namely the fidelity of chromosome segregation and occurrence of aneuploidy, as well as the clinical applications of cell cycle monitoring in human embryos.
In both mitosis and meiosis, metaphase to anaphase transition requires the activity of a ubiquitin ligase known as anaphase promoting complex/cyclosome (APC/C). The activation of APC/C in metaphase is under the control of the checkpoint mechanism, called the spindle assembly checkpoint (SAC), which monitors the correct attachment of all kinetochores to the spindle. It has been shown previously in somatic cells that exposure to a small molecule inhibitor, prodrug tosyl-l-arginine methyl ester (proTAME), resulted in cell cycle arrest in metaphase, with low APC/C activity. Interestingly, some reports have also suggested that the activity of SAC is required for this arrest. We focused on the characterization of proTAME inhibition of cell cycle progression in mammalian oocytes and embryos. Our results show that mammalian oocytes and early cleavage embryos show dose-dependent metaphase arrest after exposure to proTAME. However, in comparison to the somatic cells, we show here that the proTAME-induced arrest in these cells does not require SAC activity. Our results revealed important differences between mammalian oocytes and early embryos and somatic cells in their requirements of SAC for APC/C inhibition. In comparison to the somatic cells, oocytes and embryos show much higher frequency of aneuploidy. Our results are therefore important for understanding chromosome segregation control mechanisms, which might contribute to the premature termination of development or severe developmental and mental disorders of newborns.
The human rights and fundamental freedoms have experienced quite a dramatic development in the Czech Republic. During the short period of existence of the First Republic, the first joint state of the Czechs and Slovaks, a basis for the theory of human rights and their protection was formed and subsequently, after the fall of communism in 1989, was reincorporated into the Czech legal system. Almost immediately after the collapse of the communist regime, the Czech Parliament adopted a new Constitution, a Charter of Rights and Freedoms and a number of laws regulating the area of human rights and fundamental freedoms. The legislator not only « proclaimed » individual human rights and freedoms but also recreated a system of their protection. Human rights in the Czech legal system are given protection at both the national and international level. Under Czech constitutional law, the protection of human rights is ensured through judicial institutions, the Czech Constitutional Court, in particular, as well as through non-judicial institutions, such as the new institution of ombudsman. International protection is based on numerous international treaties regarding human rights to which the Czech Republic ratified and is a party to, including, without limitation, the European Convention on the Protection of Human Rights and Freedoms.
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