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Scientists Develop Human Embryos Through Early Post-implantation Stages

October 23, 2017

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Human embryo, 8-9 weeks, 38 mm. Graphic credit: Anatomist90 - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=18327186

Editor's note: These embryos under study were the result of egg collection and fertilization during IVF procedures.  In this procedure, often 8+ eggs are collected and fertilized. Since there is a limit as to the number of fertilized eggs that can be implanted, all excess fertilized eggs are normally destroyed. In the UK, embryos can be studied up to 14 days post fertilization. 

Last year, research enabled a new technique that allows embryos to develop in vitro beyond the implantation stage (when the embryo would normally implant into the womb). This technique has been developed by scientists at the University of Cambridge allowing them to analyze for the first time, key stages of human embryo development up to 13 days after 1) ___. The technique could open up new avenues of research aimed at helping improve the chances of success of IVF.

Once an egg has been fertilized by a 2) ___, it divides several times to generate a small, free-floating ball of stem cells. Around day three, these stem cells cluster together inside the embryo towards one side; this stage is known as the blastocyst. The blastocyst comprises three cell types: cells that will develop into the future body (which form the 'epiblast'), cells that will develop into the placenta and allow the embryo to attach to the womb, and cells that form the primitive endoderm that will ensure that the fetus's organs develop properly and will provide essential nutrients. This pre-implantation period -- so-called as the blastocyst has yet to implant itself into the 3) ___ -- has been extensively studied in human embryos using in vitro culture methods. However, on the seventh day of development, the human embryo must implant into the uterus of the mother to survive and to develop further, even though UK law permits embryos to be studied in the laboratory for up to 14 days. The failure of an embryo to implant is a major cause of early pregnancy loss and yet the cellular and molecular changes that take place in the human embryo at this stage remain unknown. This is because it is impossible to carry out such studies on embryos developing in the womb, and until now there has been no system to culture human embryos in the laboratory beyond day seven.

According to 2 papers published in Nature and Nature Cell Biology, reported the development of a technique that allows them to culture 4) ___ embryos outside the body of the mother for an additional six days, up to day 13 of development. Using the technique, the researchers have shown that the reorganization of the embryo that normally takes place during early post-implantation development can be achieved in the lab given the right culture conditions. According to the authors, implantation is a milestone in human development as it is from this stage onwards that the embryo really begins to take shape and the overall body plans are decided. It is also the stage of 5) ___ at which many developmental defects can become acquired. But until now, it has been impossible to study this in human embryos. This new technique provides a unique opportunity to get a deeper understanding of our own development during these crucial stages and help us understand what happens, for example, during miscarriage. 

The authors established a system for the in vitro culture of human embryos and, using this technique, followed the development of the embryos up to day 13 of development. Immediately following 'implantation', the three cell types that comprise the 6) ___ reorganize into a new configuration. According to the authors, The stem cells in the epiblast that will form the future body have the remarkable ability to self-organize themselves and create a cavity that represents the basic structure of the early post-implantation human embryo and that without this cavity, it would be impossible for the embryo to develop further. It is also a mechanism that we can study using human embryonic stem 7) ___. This cavity was previously thought to arise through a process known as apoptosis, or programmed cell 8) ___, but using human embryonic stem cell models, the authors were able to show that in fact cell death is not required for the cavity formation in human embryos. This process is similar to what we have recently observed in mouse embryos, despite the significant differences in the structure of post-9) ___ embryos in these different mammalian species, and suggests it may be a fundamental process conserved across many species. This research has been possible thanks to couples that underwent IVF treatment and decided to donate their surplus 10) ___ to advance our understanding of the early phases of post-implantation human development. 

The research was licensed by the UK Human Fertilization and Embryology Authority.

Source: University of Cambridge. The original story is licensed under a Creative Commons Attribution 4.0 International License.  Journal References: Nature Cell Biology, 2016; DOI: 10.1038/ncb3347; Nature, 2016; DOI: 10.1038/nature17948

Embryology: Excellent animation

ANSWERS: 1) fertilization; 2) sperm; 3) uterus; 4) human; 5) pregnancy; 6) blastocyst; 7) cells; 8) death; 9) implantation; 10) embryos

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