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cell  cleavage  culture  development  early  embryo  embryos  human  lapse  molecular  morphological  selection  time lapse  time  tls 
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Preview: Molecular Human Reproduction - current issue

Molecular Human Reproduction - current issue

Molecular Human Reproduction - RSS feed of current issue


Cell fate in animal and human blastocysts and the determination of viability


Understanding the mechanisms underlying the first cell differentiation events in human preimplantation development is fundamental for defining the optimal conditions for IVF techniques and selecting the most viable embryos for further development. However, our comprehension of the very early events in development is still very limited. Moreover, our knowledge on early lineage specification comes primarily from studying the mouse model. It is important to recognize that although mammalian embryos share similar morphological landmarks, the timing and molecular control of developmental events may vary substantially between species. Mammalian blastocysts comprise three cell types that arise through two sequential rounds of binary cell fate decisions. During the first decision, cells located on the outside of the developing embryo form a precursor lineage for the embryonic part of the placenta: the trophectoderm and cells positioned inside the embryo become the inner cell mass (ICM). Subsequently, ICM cells differentiate into embryonic lineages that give rise to a variety of tissues in the developing foetus: either the epiblast or extraembryonic primitive endoderm. Successful formation of all three lineages is a prerequisite for implantation and development to term. A comprehensive understanding of the lineage specification processes in mammals is therefore necessary to shed light on the causes of early miscarriages and early pregnancy pathologies in humans.

Polarity and cell division orientation in the cleavage embryo: from worm to human


Cleavage is a period after fertilization, when a 1-cell embryo starts developing into a multicellular organism. Due to a series of mitotic divisions, the large volume of a fertilized egg is divided into numerous smaller, nucleated cells—blastomeres. Embryos of different phyla divide according to different patterns, but molecular mechanism of these early divisions remains surprisingly conserved. In the present paper, we describe how polarity cues, cytoskeleton and cell-to-cell communication interact with each other to regulate orientation of the early embryonic division planes in model animals such as Caenorhabditis elegans, Drosophila and mouse. We focus particularly on the Par pathway and the actin-driven cytoplasmic flows that accompany it. We also describe a unique interplay between Par proteins and the Hippo pathway in cleavage mammalian embryos. Moreover, we discuss the potential meaning of polarity, cytoplasmic dynamics and cell-to-cell communication as quality biomarkers of human embryos.

Assessment of human embryo development using morphological criteria in an era of time-lapse, algorithms and 'OMICS: is looking good still important?


With the worldwide move towards single embryo transfer there has been a renewed focus on the requirement for reliable means of assessing embryo viability. In an era of ‘OMICS’ technologies, and algorithms created through the use of time-lapse microscopy, the actual appearance of the human embryo as it progresses through each successive developmental stage to the blastocyst appears to have been somewhat neglected in recent years. Here we review the key features of the human preimplantation embryo and consider the relationship between morphological characteristics and developmental potential. Further, the impact of the culture environment on morphological traits, how key morphological qualities reflect aspects of embryo physiology, and how computer-assisted analysis of embryo morphology may facilitate a more quantitative approach to selection are discussed. The clinical introduction of time-lapse systems has reopened our eyes and given us a new vantage point from which to view the beauty of the initial stages of human life. Rather than a future in which the morphology of the embryo is deemed irrelevant, we propose that key features, such as multinucleation, cell size and blastocyst differentiation should be included in future iterations of selection/deselection algorithms.

How much have we learned from time-lapse in clinical IVF?


Can the time-lapse system (TLS) identify the best embryo for transfer? Although there are several studies that support this hypothesis, more research is required to improve the quality of the current evidence and also to assess live birth rate, miscarriage, stillbirth or clinical pregnancy in order to choose between a TLS or conventional incubation. In addition, although some authors report on effectiveness and safety in the use of TLS monitoring of embryo development in vitro, other authors that have not found relevant differences between the two systems for the culture and subsequence embryo selection. On the other hand, TLS has emerged as a novel technology and has been introduced into clinical practice in many laboratories to perform embryo morphology evaluation and study developmental kinetics in ART. However, most studies only assess blastocyst formation or implantation rate as the primary end-point and additional data are required, for example, about live birth, monozygotic twinning rates and health problems. Furthermore, the features of populations studies are varied; for example, female and male age, seminal characteristics and female factor. The embryo culture conditions and culture medium used also vary. For this review, a search of PubMed was conducted to retrieve relevant studies regarding use of TLS in embryo incubation and selection, and compare them with standard embryo culture and evaluation.