但卻可對胚胎之動態生理學提供更進一步精確之瞭解
包括胚胎分裂立體結構，分裂平面，胚葉細胞相對位置‧
而不僅僅只了解胚胎分裂之速度，胚葉細胞之數量
Cleavage in the preimplantation embryo: it is all about being in the right place at the right time!
+Author Affiliations
- ↵*Correspondence address. E-mail: dsakkas@bostonivf.com
- Received August 22, 2016.
- Revision received August 22, 2016.
- Accepted August 24, 2016.
In this special review edition of Molecular Human Reproduction, we examine the impact of cell cleavage timing and morphology on the viability of preimplantation embryos. The concept of cleavage timing and morphology is brought into relevance by initially examining how cleavage planes, position and number in the early cleavage embryo impact developmental potential in different models, from flies to human. Finally, the historical use of cleavage assessment and morphology in human IVF in addition to the current clinical use of time-lapse imaging is discussed.
Preimplantation embryo morphology and the timing of cleavage has been a mainstay for the clinical embryologist in human IVF. In the first reported case of IVF and embryo development in the human, Rock and Menkin (1944) made the following observation about the developing fertilized embryo: ‘One of these (embryo), when first seen in cleavage, consisted of one large blastomere and two smaller ones, each of the three containing a round, vesicular nucleus. The second egg from this same patient was in a similar stage, but part of the cytoplasm appeared fragmented, and soon proceeded to undergo rapid degenerative changes.’
Since that first observation, embryologists working in the field of IVF have relied largely on examining the morphology and timing of embryo development to select the best embryo.
The underlying importance of these two observations has, however, not always been appreciated and the need of the cells within the embryo to cleave in the correct manner and to be in the right place at the right time has sometimes been overlooked by the clinical embryologist.
The first two reviews (Ajduk and Zernicka-Goetz, 2016; Piliszek et al. 2016) examine the question of ‘Is the way a cell divides and where it goes important?’ In these reviews, we gain a better insight into how cleavage patterns impact molecular expression patterns and subsequent viability in species that have a more definitive animal and vegetal pole. We learn that despite the diversity in cleavage patterns between phyla, the molecular mechanisms regulating early embryonic divisions remain strongly conserved. The concept that cleavage division can lead to cells of not only different sizes but inherently different components is introduced and how this ultimately causes cells to follow distinct developmental paths. The observation of how the viability of a mouse embryo is affected by the pattern of segregation and inheritance of material from the daughter blastomere which undergoes at least one meridional division sheds light on the subtle importance of correct cleavage (Ajduk and Zernicka-Goetz, 2016). Piliszek et al. (2016) also discuss cell fate in mouse and human blastocysts again highlighting the importance of cells being in the correct place at the right time. This impacts the concept of just scoring blastocysts in human IVF and highlights the question: are we missing aspects of their development by just scoring expansion, inner cell mass and trophectoderm? The importance of cell positioning in the blastocyst also leads to questions of how much information we can glean from a trophectoderm biopsy when performing preimplantation genetic screening.
In the third review, Gardner and Balaban (2016), the key features of the human preimplantation embryo are considered in light of historical data on the relationship between morphological characteristics and developmental potential. They argue that these observations have not only taught us about embryo potential, but also inform us about the impact of the culture environment on morphological traits and how key morphological qualities reflect aspects of embryo physiology.
The importance of these observations has been an ongoing discussion for human embryos; however, it has now come under more scrutiny with the advent of video imaging or time-lapse systems. The final review from the group of Meseguer (Motato et al., 2016) discusses how time-lapse systems have provided us with a multitude of data which are now being used to track cleavage patterns and timing more precisely. They show how time-lapse systems have taken the evaluation of embryo morphology and developmental kinetics to another level and how it is starting to impact clinical practice. Unfortunately, however, further studies are required to improve the quality of the current evidence.
Our excitement in being able to visualize the preimplantation human embryo in its first few days of development using time-lapse systems is best summarized by Gardner and Balaban (2016), who stated that ‘it has reopened our eyes and given us a new vantage from which to view the beauty of the initial stages of human life’.
By assessing the scientific evidence in different species that relates the viability of an embryo to its early cleavage planes, timing and position, we hope to enlighten readers to think in novel ways regarding how to approach the use of this information. In many ways, we have tackled the analysis of this data with the concepts that we have used historically, using cell number and time. The non-human studies from the fly to the mouse tell us that it is not only number and time but that other aspects are crucial. A deeper analysis of the time-lapse data will in the future allow us to develop algorithms which assimilate not only cell number and time but more components, including the cleavage plane and position of each cell. This data will help us more accurately predict not only which embryo will lead to a healthy live birth, but also provide insights into the genomic and metabolic tendencies of each individual embryo.
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