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• W2548150841 abstract "Cytoplasmic fragmentation is the most common cause of embryonic loss after in vitro fertilizationand culture of human eggs. The occurrence of fragmentation often coincides with the presence ofother abnormalities, including low cell number, uneven blastomere size, disrupted cell-cell contact,blastomere multi-nucleation, and chaotic chromosome mosaicism. As commonly as fragmentationis observed during clinical practice of in vitro fertilization and embryo transfer, the phenomenonitself rarely has been studied. The occasional investigative attempts have narrowly focusedon linking fragmentation to apoptosis. Undoubtedly, one reason for this limited inquiry is thepractical difficulties and obstacles associated with the use of human eggs and embryos for experimentation.The lack of a suitable animal model and the relative unimportance of fragmentationin experimental mouse embryology have also contributed to its dismissal as a worthy researchsubject. The present studies aim to reach beyond these imposed and inherent limitations and uncoverthe causes and mechanisms of cytoplasmic fragmentation, and delineate its developmentalconsequences. Chapter 3 describes a fragmentation classification system which was developedthrough non-invasive morphological evaluation of large numbers of embryos and was based onfragmentation patterns: the size and distribution of fragments relative to the size and position ofnucleated cells. These patterns along with (but independent of) the degree of fragmentation wereshown to be of predictive value for clinical outcome of in vitro fertilization and embryo transferand therefore useful for selection of embryos for transfer. The loss of more than one third of thecytoplasmic volume to fragmentation or formation of large fragments was found to lead to a significantdecrease in implantation and pregnancy rates following intrauterine transfer on day-3 ofdevelopment. In Chapter 4, embryos with fragmentation and other abnormalities were followedthrough day-S of development in culture; it was discovered that the processes of compaction,cavitation, and blastulation were often abnormal in such embryos. In Chapters 5 and 6, attemptswere made to discover whether (and how) fragments interfered with development. It was shown ina mouse model that continued development of blastomeres was generally unaffected by the presenceof fragments. In the human, isolation of intact blastomeres from several fragmented embryosand their aggregation within a host zona pellucida led regularly to formation of chimaeric blastocysts.This work demonstrated that viable cells with apparently normal regulatory capacity canbe found within non-viable embryos. In Chapter 7, the distribution of a vital cell adhesion protein,E-cadherin, was investigated in abnormal embryos by immunocytochemistry and confocalfluorescence microscopy. The results suggested that the characteristic distribution pattern of Ecadherinis perturbed and erratic in such embryos, providing one explanation for their failure tocompact, cavitate or blastulate normally. Finally, the experiments described in Chapter 8 revealedthe key to the nature of fragmentation: its resemblance to cytokinesis in its requirement for activation,its timing in the cell cycle, and its mediation by reorganization of the cytoskeleton. This wasinvestigated in a mouse model, using enucleation as a way to make eggs and embryos fragmentation-prone': In meiotic cells, the timing of fragmentation coincided with second polar body extrusion,and in mitotic cells, it coincided with mitosis and cell division. Therefore, far from beingrandom, fragmentation occurred only during theM phase of the cell cycle. By taking into considerationthe observation that the non-activated mature eggs neither divide nor fragment and thatsuch eggs are arrested in metaphase, it was also possible to point to cytokinesis as the phase duringwhich fragmentation occurs. The close association of fragmentation with the M phase of thecell division cycle, and in particular with the failing coordination of microtubule function wouldaccount for the numerous chromosomal and nuclear abnormalities that accompany fragmentation.Furthermore, by firmly establishing a link between fragmentation and cell division, both nuclearand cytoplasmic, the present work has definitively opened an important area for future research, mostcritically, into strategies to minim.ize or prevent fragmentation and its associated abnormalities." @default.
• W2548150841 created "2016-11-11" @default.
• W2548150841 creator A5042713796 @default.
• W2548150841 date "2017-01-05" @default.
• W2548150841 modified "2023-09-27" @default.
• W2548150841 title "On fragmentation: origin and consequences of abnormal cell division in human embryos in vitro" @default.
• W2548150841 doi "https://doi.org/10.4225/03/586f4e0c9e019" @default.
• W2548150841 hasPublicationYear "2017" @default.
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