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Journal Technologies of Living Systems №1 for 2017 г.
Article in number:
Modern views on the compaction of the human embryo in vitro
Keywords: in vitro fertilization embryo embryo compaction morula embryogenesis
Authors:
E.V. Kovalskaya - Embryologist, Department of Assistive Reproductive Technology in the Treatment of In-fertility Research Center of Obstetrics, Gynecology and Perinatology (Moscow) E-mail: e_kovalskaya@oparina4.ru A.G. Syrkasheva - Ph.D. (Med.), Research Scientist, ART Department, Research Center for Obstetrics, Gynecology and Perinatology (Moscow) E-mail: anast.syrkasheva@gmail.com A.Yu. Romanov - Clinical Resident, Research Center for Obstetrics, Gynecology and Perinatology (Moscow) E-mail: romanov1553@yandex.ru N.P. Makarova - Ph.D. (Med.), Senior Research Scientist, Department of Assistive Reproductive Technology in the Treatment of Infertility Research Center of Obstetrics, Gynecology and Perinatology (Moscow) E-mail: np_makarova@oparina4.ru N.V. Dolgushina - Dr.Sc. (Med.), Associate Professor, Head of R&D Department, Research Center for Obstetrics, Gynecology and Perinatology (Moscow) E-mail: n_dolgushina@oparina4.ru
Abstract:
The aim of this review was to summarize current data on one of the key stages of early embryogenesis - morula formation. It is known, that morula formation occurs in 72-80 hours after fertilization. But factors influencing this process are still not well established. Blastomeric morphology has no visible differences during first cleavage stages. In mice, embryo compaction begins at the 8-cell stage, in humans - at the 8 and up to 16-cell stage. Morphological sign of compaction is the thickening of individual blastomeres and increase of the contact area between adjacent cells. Extra- and intracellular organization changes include blastomeres polarization, cell-cell contacts formation and cytoskeletal interactions between blastomeres. Intercellular junctions Several types of cell-cell contacts are generated and participate in morula formation: gap, adherence, tight junctions and desmosomes. They play an important role in cell-cell interactions, adhesion and embryo differentiation. Gap junctions in the human embryo may first appear at 4-cell stage as well as later. The building block of gap junction is the connexin protein. Six connexin molecules form connexon and two neighboring cells connexons make an intracellular channel. These transmembrane pores enable interaction between adjacent cells through a transport of metabolites and regulatory molecules. Injection of anti-connexin antibodies in mouse embryos leads to disruption of compaction while maintaining the blastomeres cytokinesis ability. Adherens junctions contain Ca2+-dependent transmembrane glycoprotein called E-cadherin. On the 4th day of development these proteins move into the area of cell-cell contacts. E-cadherin redistribution is either not observed or random when compaction is abnormal or absent. Tight junctions connect adjacent cell membranes. In mice, tight junctions arise at 8-cell stage to provide the tightness be-tween cells and maintain cell polarity. Desmosomes are small disk-shaped contacts, formed by transmembrane molecules (desmocollin and desmoglein), desmo-somes connect the epithelial cells. In human embryos desmosomes begin to appear at 16-cell stage and their number in-creases dramatically during cavitation. Carbohydrate antigens, for example, SSEA-1 can also be involved in the compaction process. Genome activation and epigenetic control Compaction of the 8-cell stage embryo marks the beginning of the blastocyst formation and normally leads to loss of toti-potency of blastomeres, the differentiation of the trophectoderm and the inner cell mass, which is considered an embryonic genome activation by some authors. Compaction of mouse embryos is faster in polyploid embryos, which indirectly indicates the involvement of the embryo genome in the compaction process. Preimplantation embryo development is regulated genetically and epigenetically (gene methylation and histone modifications). Nuclear-cytoplasmic ratio changes during divi-sion cycles can possibly trigger embryo compaction. Factors influencing the process of embryo compaction In vitro embryo development may be affected by the culture medium volume and components, their by-products, the number of embryos cultured in the culture medium, the gases concentrations and the pH of the culture medium. Since some elements of cell-cell contacts are cation-dependent, it is considered, that Ca2+ and Mg2+ ions are necessary for compaction. Morula can be decompacted by placing it in a deionized medium for a few minutes. Morphokinetic data on the embryo compaction Use of time-lapse observation technologies in assisted reproduction demonstrated timeslots for normal embryo development. But these observations vary for different groups of researchers. That is why the issue of premature or slow embryo compaction requires close attention of clinical embryologists.
Pages: 25-35
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