I-35: Genetic Aberrations in Early Development:The Origins and The Fates

Genetic aberrations are commonly seen in human preimplantation embryos. Non-disjunction and premature division of a chromosome are common in both meiosis and mitosis divisions. The expected result for meiotic aneuploidies is full aneuploidy in the later stages whereas mosaicism is the most frequent event in the cleavage and blastocyst stages. The main causes for mosaicism are post-zygotic events during early mitotic divisions of the embryo most particularly at the cleavage stage because of genome activation by third cell division. Segmental chromosome aneuploidies following chromosome breakage, blastomeres fusion and errors in cytokinesis are frequent events in the cleavage stage. Changes in culture conditions and hormonal stimulation protocols could affect chromosome segregation. Diploidaneuploid mosaicism is the most frequent abnormality observed in preimplantation stage. The analysis of a number of cells cannot guarantee omission of all mosaic embryos; hence, embryos selected by preimplantation genetic diagnosis at the cleavage or blastocyst stage could be partly abnormal. Several reasons have been proposed for self-correction of aneuploidies during later stages of development including primary misdiagnosis, allocation of the aneuploidy in the trophectoderm, cell growth advantage of diploid cells in mosaic embryos, lagging of aneuploid cell division, extrusion or duplication of an aneuploid chromosome, and the abundance of DNA repair gene products. Differentiation is known as the barrier for eliminating mosaic embryos by death and/or decreased division of abnormal cells, there would be selection based on the type and rate of mosaicism in each cell line. However some mosaicisms, such as copy number variations could be compatible with live birth and might result in differentiation advantage. The genetic difference between discordant monozygotic twins provides evidence for such mosaicisms. There are three outcomes for mosaic embryos following differentiation: abortions, birth defects and healthy newborns. Self-correction may rarely occur as a result of the advantage that diploid cells have for survival and division. More information will be discussed in this presentation.