Control mechanisms of spindle assembly and chromosome segregation are vital for preventing aneuploidy during cell division. The mammalian germ cells and embryos are prone to chromosome segregation errors, and the resulting aneuploidy is a major cause of termination of development or severe developmental disorders. Here we focused on early mouse embryos, and using combination of methods involving microinjection, immunodetection and confocal live cell imaging, we concentrated on the Spindle Assembly Checkpoint (SAC) and Anaphase Promoting Complex/Cyclosome (APC/C). These are two important mechanisms cooperating during mitosis to ensure accurate chromosome segregation, and assessed their activity during the first two mitoses after fertilization. Our results showed, that in zygotes and 2-cell embryos, the SAC core protein Mad1 shows very low levels on kinetochores in comparison to oocytes and its interaction with chromosomes is restricted to a short time interval after nuclear membrane disassembly (NEBD). Exposure of 2-cell embryos to low levels of spindle poison does not prevent anaphase, despite the spindle damage induced by the drug. Lastly, the APC/C is activated coincidentally with NEBD before the spindle assembly completion. This early onset of APC/C activity, together with precocious relocalization of Mad1 from chromosomes, prevents proper surveillance of spindle assembly by SAC. The results contribute to the understanding of the origin of aneuploidy in early embryos.

• Klíčová slova
• Mad1, anaphase, anaphase-promoting complex, chromosome segregation, embryo, spindle, spindle assembly checkpoint,
• Publikační typ
• časopisecké články MeSH

Chromosome segregation in female germ cells and early embryonic blastomeres is known to be highly prone to errors. The resulting aneuploidy is therefore the most frequent cause of termination of early development and embryo loss in mammals. And in specific cases, when the aneuploidy is actually compatible with embryonic and fetal development, it leads to severe developmental disorders. The main surveillance mechanism, which is essential for the fidelity of chromosome segregation, is the Spindle Assembly Checkpoint (SAC). And although all eukaryotic cells carry genes required for SAC, it is not clear whether this pathway is active in all cell types, including blastomeres of early embryos. In this review, we will summarize and discuss the recent progress in our understanding of the mechanisms controlling chromosome segregation and how they might work in embryos and mammalian embryos in particular. Our conclusion from the current literature is that the early mammalian embryos show limited capabilities to react to chromosome segregation defects, which might, at least partially, explain the widespread problem of aneuploidy during the early development in mammals.

• Klíčová slova
• CDK1, aneuploidy, cell size, chromosome division, embryo, segregation errors, spindle, spindle assembly checkpoint,
• MeSH
• aneuploidie MeSH
• chromozomy MeSH
• embryonální vývoj * genetika   MeSH
• lidé MeSH
• savci genetika   MeSH
• segregace chromozomů * MeSH
• velikost buňky MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

In pigs, in vitro production is difficult with a high occurrence of polyspermy and low blastocyst formation rates. To test the hypothesis that this may, at least in part, be due to chromosomal errors, we employed whole genome amplification and comparative genomic hybridization, performing comprehensive chromosome analysis to assess both cells of the two-cell stage in vitro porcine embryos. We thus described the incidence, nature and origin of chromosome abnormalities, i.e. whether they derived from incorrect meiotic division during gametogenesis or aberrant mitotic division in the zygote. We observed that 19 out of 51 (37%) of two-cell stage early pig IVP embryos had a chromosome abnormality, mostly originating from an abnormal division in the zygote. Moreover, we frequently encountered multiple aneuploidies and segmental chromosome aberrations. These results indicate that the pig may be particularly sensitive to in vitro production, which may, in turn, be due to incorrect chromosome segregations during meiosis and early cleavage divisions. We thus accept our hypothesis that chromosome abnormality could explain poor IVP outcomes in pigs.

• Klíčová slova
• Aneuploidy, Comparative genomic hybridization, Embryo, Pig,
• MeSH
• aneuploidie MeSH
• chromozomální aberace * MeSH
• embryo savčí MeSH
• fertilizace in vitro veterinární   MeSH
• srovnávací genomová hybridizace MeSH
• Sus scrofa embryologie   genetika   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH