̽��ֱ�� of Cambridge - embryo

̽��ֱ��Vice-Chancellor's Awards 2023 for Research Impact and Engagement

zs332 — Wed, 13 Dec 2023 09:20:46 +0000

Meet the winner of the Vice-Chancellor's Awards 2023 for Research Impact and Engagement and learn more about their projects.

Human embryo-like models created from stem cells to understand earliest stages of human development

cjb250 — Tue, 27 Jun 2023 15:00:04 +0000

Published today in the journal Nature, this embryo model is an organised three-dimensional structure derived from pluripotent stem cells that replicate some developmental processes that occur in early human embryos.

Use of such models allows experimental modelling of embryonic development during the second week of pregnancy. They can help researchers gain basic knowledge of the developmental origins of organs and specialised cells such as sperm and eggs, and facilitate understanding of early pregnancy loss.

“Our human embryo-like model, created entirely from human stem cells, gives us access to the developing structure at a stage that is normally hidden from us due to the implantation of the tiny embryo into the mother’s womb,” said Professor Magdalena Zernicka-Goetz in the ̽��ֱ�� of Cambridge’s Department of Physiology, Development and Neuroscience, who led the work.

She added: “This exciting development allows us to manipulate genes to understand their developmental roles in a model system. This will let us test the function of specific factors, which is difficult to do in the natural embryo.”

In natural human development, the second week of development is an important time when the embryo implants into the uterus. This is the time when many pregnancies are lost.

̽��ֱ��new advance enables scientists to peer into the mysterious ‘black box’ period of human development – usually following implantation of the embryo in the uterus – to observe processes never directly observed before.

Understanding these early developmental processes holds the potential to reveal some of the causes of human birth defects and diseases, and to develop tests for these in pregnant women.

Until now, the processes could only be observed in animal models, using cells from zebrafish and mice, for example.

Legal restrictions in the UK currently prevent the culture of natural human embryos in the lab beyond day 14 of development: this time limit was set to correspond to the stage where the embryo can no longer form a twin.

Until now, scientists have only been able to study this period of human development using donated human embryos. This advance could reduce the need for donated human embryos in research.

Zernicka-Goetz says the while these models can mimic aspects of the development of human embryos, they cannot and will not develop to the equivalent of postnatal stage humans.

Over the past decade, Zernicka-Goetz’s group in Cambridge has been studying the earliest stages of pregnancy, in order to understand why some pregnancies fail and some succeed.

In 2021 and then in 2022 her team announced in Developmental Cell, Nature and Cell Stem Cell journals that they had finally created model embryos from mouse stem cells that can develop to form a brain-like structure, a beating heart, and the foundations of all other organs of the body.

̽��ֱ��new models derived from human stem cells do not have a brain or beating heart, but they include cells that would typically go on to form the embryo, placenta and yolk sac, and develop to form the precursors of germ cells (that will form sperm and eggs).

Many pregnancies fail at the point when these three types of cells orchestrate implantation into the uterus begin to send mechanical and chemical signals to each other, which tell the embryo how to develop properly.

There are clear regulations governing stem cell-based models of human embryos and all researchers doing embryo modelling work must first be approved by ethics committees. Journals require proof of this ethics review before they accept scientific papers for publication. Zernicka-Goetz’s laboratory holds these approvals.

“It is against the law and FDA regulations to transfer any embryo-like models into a woman for reproductive aims. These are highly manipulated human cells and their attempted reproductive use would be extremely dangerous,” said Dr Insoo Hyun, Director of the Center for Life Sciences and Public Learning at Boston’s Museum of Science and a member of Harvard Medical School’s Center for Bioethics.

Zernicka-Goetz also holds position at the California Institute of Technology and is NOMIS Distinguished Scientist and Scholar Awardee.

̽��ֱ��research was funded by the Wellcome Trust and Open Philanthropy.

Reference
Weatherbee, B A T et al.: A model of the post-implantation human embryo derived from pluripotent stem cells. Nature; 27 June 2023. DOI: 10.1038/s41586-023-06368-y

Cambridge scientists have created a stem cell-derived model of the human embryo in the lab by reprogramming human stem cells. ̽��ֱ��breakthrough could help research into genetic disorders and in understanding why and how pregnancies fail.

Our human embryo-like model gives us access to the developing structure at a stage that is normally hidden from us due to the implantation of the tiny embryo into the mother’s womb

Magdalena Zernicka-Goetz

̽��ֱ�� of Cambridge

Day 4 embryoid showing an inner epiblast like domain in magenta that has apico-basal polarity (yellow apical, blue basal), similar to the epiblast of the human embryo just after implantation

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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"Reproduction matters to us all": latest issue of Horizons magazine

lw355 — Fri, 20 Nov 2020 11:26:45 +0000

Professor Kathy Niakan talks about why it’s vital to take a multidisciplined approach to understanding the urgent challenges posed by reproduction today – and introduces our Spotlight on some of this work, highlighted in the latest issue of Cambridge's Horizons magazine.

Study suggests embryos could be susceptible to coronavirus as early as second week of pregnancy

cjb250 — Tue, 04 Aug 2020 23:22:16 +0000

̽��ֱ��researchers say this could mean embryos are susceptible to COVID-19 if the mother gets sick, potentially affecting the chances of a successful pregnancy.

While initially recognised as causing respiratory disease, the SARS-CoV-2 virus, which causes COVID-19 disease, also affects many other organs. Advanced age and obesity are risk factors for complications but questions concerning the potential effects on fetal health and successful pregnancy for those infected with SARS-CoV-2 remain largely unanswered.

To examine the risks, a team of researchers used technology developed by Professor Magdalena Zernicka-Goetz at the ̽��ֱ�� of Cambridge to culture human embryos through the stage they normally implant in the body of the mother to look at the activity – or ‘expression’ – of key genes in the embryo. Their findings are published today in the Royal Society’s journal Open Biology.

On the surface of the SARS-CoV-2 virus are large ‘spike’ proteins. Spike proteins bind to ACE2, a protein receptor found on the surface of cells in our body. Both the spike protein and ACE2 are then cleaved, allowing genetic material from the virus to enter the host cell. ̽��ֱ��virus manipulates the host cell’s machinery to allow the virus to replicate and spread.

̽��ֱ��researchers found patterns of expression of the genes ACE2, which provide the genetic code for the SARS-CoV-2 receptor, and TMPRSS2, which provides the code for a molecule that cleaves both the viral spike protein and the ACE2 receptor, allowing infection to occur. These genes were expressed during key stages of the embryo’s development, and in parts of the embryo that go on to develop into tissues that interact with the maternal blood supply for nutrient exchange. Gene expression requires that the DNA code is first copied into an RNA message, which then directs the synthesis of the encoded protein. ̽��ֱ��study reports the finding of the RNA messengers.

Professor Magdalena Zernicka-Goetz, who holds positions at both the ̽��ֱ�� of Cambridge and Caltech, said: “Our work suggests that the human embryo could be susceptible to COVID-19 as early as the second week of pregnancy if the mother gets sick.

“To know whether this really could happen, it now becomes very important to know whether the ACE2 and TMPRSS2 proteins are made and become correctly positioned at cell surfaces. If these next steps are also taking place, it is possible that the virus could be transmitted from the mother and infect the embryo’s cells.”

Professor David Glover, also from Cambridge and Caltech, added: “Genes encoding proteins that make cells susceptible to infection by this novel coronavirus become expressed very early on in the embryo’s development. This is an important stage when the embryo attaches to the mother’s womb and undertakes a major remodelling of all of its tissues and for the first time starts to grow. COVID-19 could affect the ability of the embryo to properly implant into the womb or could have implications for future fetal health.”

̽��ֱ��team say that further research is required using stem cell models and in non-human primates to better understand the risk. However, they say their findings emphasise the importance for women planning for a family to try to reduce their risk of infection.

“We don’t want women to be unduly worried by these findings, but they do reinforce the importance of doing everything they can to minimise their risk of infection,” said Bailey Weatherbee, a PhD student at the ̽��ֱ�� of Cambridge.

Reference
Weatherbee, BAT, et al. Expression of SARS-CoV-2 receptor ACE2 and the protease TMPRSS2 suggests susceptibility of the human embryo in the first trimester. Open Biology; 5 Aug 2020; DOI: 10.1098/rsob.200162

Image
Image of a human embryo cultured in vitro through the implantation stages and stained to reveal OCT4 transcription factor, magenta; GATA6 transcription factor, white; F-actin, green; and DNA, blue. Analysis of patterns of gene expression in such embryos reveals that ACE2, the receptor for the SARS-CoV-2 virus, and the TMPRSS2 protease that facilitates viral infection are expressed in these embryos, which represent the very early stages of pregnancy. (Credit: Zernicka-Goetz Lab)

Genes that are thought to play a role in how the SARS-CoV-2 virus infects our cells have been found to be active in embryos as early as during the second week of pregnancy, say scientists at the ̽��ֱ�� of Cambridge and the California Institute of Technology (Caltech).

COVID-19 could affect the ability of the embryo to properly implant into the womb or could have implications for future fetal health

David Glover

Zernicka-Goetz Lab

human embryo cultured in vitro

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Scientists develop mouse ‘embryo-like structures’ with organisation along body’s major axes

cjb250 — Wed, 03 Oct 2018 17:00:21 +0000

̽��ֱ��definitive architecture of the mammalian body is established shortly after the embryo implants into the uterus. This body plan has spatial references, or axes, that guide the emergence of tissues and organs: an antero-posterior axis defined by the head at one end and the tail at the other, an orthogonal dorso-ventral axis and a medio-lateral axis, which orientates the arrangement of internal organs like the liver, pancreas or the heart.

Studying the processes orchestrating the formation of early mammalian embryos is hampered by the difficulty in obtaining them. Earlier findings from the Cambridge group had shown that embryonic stem cells could self-organise in culture into structures with an antero-posterior polarity.

Now, in collaboration with researchers from the ̽��ֱ�� of Geneva and the Swiss Federal Institute of Technology Lausanne (EPFL), they have extended the cultures to reveal a capacity of mouse stem cells to produce ‘pseudo-embryos’ that display some of the important characteristics of a normal mouse embryo. Established from only 300 embryonic stem cells, these structures, called ‘gastruloids’, exhibit developmental features and organisation comparable to the posterior part of a six to ten day-old embryo.

̽��ֱ��study shows that gastruloids organise themselves with regard to the three main body axes, as they do in embryos, and follow similar patterns of gene expression. One example of this is the pattern of expression of Hox genes, an ensemble of genes that are expressed in a precise sequential order in the embryo and act as landmarks for different aspects of the body, including the position of different vertebrae or of limbs. This degree of organisation makes gastruloids a remarkable system for the study of the early stages of normal or abnormal embryonic development in mammals.

“These results significantly extend our earlier findings. We were surprised to see how far gastruloids develop, their complex organisation and the presence of early-stage tissues and organ,” says Professor Alfonso Martinez Arias, leader of the ̽��ֱ�� of Cambridge team, at its Department of Genetics.

Professor Denis Duboule from the ̽��ֱ�� of Geneva and at the EPFL explained, “To determine whether gastruloids organise themselves into bona fide embryonic structures, we characterised their level of genetic activity at different stages of development”.

̽��ֱ��researchers identified and quantified the RNA transcribed from gastruloids and compared the expressed genes with those of mouse embryos at comparable stages of development, which showed there was a high degree of similarity.

“Gastruloids form structures similar to the posterior part of the embryo, from the base of the brain to the tail, whose development program is somewhat different from that of the head,” says Dr Leonardo Beccari, co-first author of the study, from the ̽��ֱ�� of Geneva.

These embryo-like structures express genes characteristic of the various types of progenitor cells necessary for the constitution of future tissues.

“ ̽��ֱ��complexity of gene expression profiles increases over time, with the appearance of markers from different embryonic cell lineages, much like the profiles observed in control embryos,” adds Dr Naomi Moris from the Cambridge team, co-first author of the article.

“ ̽��ֱ��implementation of the Hox gene network over time, which mimics that of the embryo, particularly confirms the remarkably high level of self-organisation of gastruloids,” explains Mehmet Girgin, co-first author of the study and PhD student at the Institute of Bioengineering at EPFL.

̽��ֱ��researchers say that these pseudo-embryos will allow an alternative method to animal research, in accordance with the principle of the ‘3Rs’ (the reduction, replacement and refinement of the use of animals in research). ̽��ֱ��finding that so much of the development of an embryo can be recapitulated using stem cells will also increase researchers’ ability to study the genetic mechanisms underlying normal development and disease.

Earlier in the year, the group led by Professor Magdalena Zernicka-Goetz at the Department of Physiology, Development and Neuroscience at the ̽��ֱ�� of Cambridge reported embryo-like structures capable of generating an anteroposterior axis but which required additional, extra-embryonic, stem cells to generate anteroposterior polarity. ̽��ֱ��new work shows surprisingly that stem cells can self-organise the three axes independently of the extra-embryonic tissues.

“It makes things much simpler for research,” says Professor Martinez Arias. “Not only do gastruloids self-organise to generate the three axes, but they also mimic the spatial and temporal patterns of embryos, without extra-embryonic tissue. This suggests that gastruloids can become a useful tool, particularly in understanding gene expression during development.”

This work was largely funded by the Biotechnology and Biological Sciences Research Council (BBSRC), the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), the Engineering and Physical Sciences Research Council (EPSRC) and the European Research Council.

Adapted from a press release from the ̽��ֱ�� of Geneva.

Reference
Beccari, L, Moris, N, Girgin, M, et al. Multi-axial self-organisation properties of mouse embryonic stem cells into gastruloids. Nature; 3 Oct 2018; DOI: 10.1038/s41586-018-0578-0

Image caption
Seven-day old gastruloid. ̽��ֱ��cell nuclei are marked in blue. Neural progenitor cells (green) are distributed along the antero-posterior axis. Progenitor cells of the tail bud (pink) are confined to the posterior extremity of the gastruloid and indicate the direction of its elongation. © Mehmet Girgin, EPFL

A team of scientists at the ̽��ֱ�� of Cambridge has developed an artificial mouse embryo-like structure capable of forming the three major axes of the body. ̽��ֱ��technique, reported today in the journal Nature, could reduce the use of mammalian embryos in research.

We were surprised to see how far gastruloids develop, their complex organisation and the presence of early-stage tissues and organ

Alfonso Martinez Arias

Mehmet Girgin, EPFL

Seven-day old gastruloid

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Scientists generate key life event in artificial mouse ‘embryo’ created from stem cells

cjb250 — Mon, 23 Jul 2018 15:00:29 +0000

̽��ֱ��team, led by Professor Magdalena Zernicka-Goetz at the ̽��ֱ�� of Cambridge, previously created a much simpler structure resembling a mouse embryo in culture, using two types of stem cells – the body’s ‘master cells’ – and a 3D scaffold on which they can grow.

Now, in a study published today in Nature Cell Biology, Professor Zernicka-Goetz and colleagues have developed the embryo-like structures further, using not just two but three types of stem cells which let them reconstruct a process known as gastrulation, an essential step in which the embryonic cells being self-organising into the correct structure for an embryo to form.

Once a mammalian egg has been fertilised by a sperm, it divides multiple times to generate a small, free-floating ball comprising three types of stem cells. At the stage of development known as the ‘blastocyst’ stage, the particular stem cells that will eventually make the future body – the embryonic stem cells (ESCs) – cluster together inside the embryo towards one end. ̽��ֱ��other two types of stem cell in the blastocyst are the extra-embryonic trophoblast stem cells (TSCs), which will form the placenta, and primitive endoderm stem cells (PESCs) that will form the yolk sac, ensuring that the foetus’s organs develop properly and providing essential nutrients.

In March 2017, Professor Zernicka-Goetz and colleagues published a study that described how, using a combination of genetically-modified mouse ESCs and TSCs, together with a 3D ‘jelly’ scaffold known as an extracellular matrix, they were able to grow a structure capable of assembling itself and whose development and architecture very closely resembled the natural embryo. There was a remarkable degree of communication between the two types of stem cell: in a sense, the cells were telling each other where in the embryo to place themselves.

However, a key step in the life of the embryo – gastrulation, described by the eminent biologist Lewis Wolpert as “truly the most important time in your life” – was missing. Gastrulation is the point at which the embryo transforms from being a single layer to three layers: an inner layer (endoderm), middle layer (mesoderm) and outer layer (endoderm), determining which tissues or organs the cells will then develop into.

“Proper gastrulation in normal development is only possible if you have all three types of stem cell. In order to reconstruct this complex dance, we had to add the missing third stem cell,” says Professor Zernicka-Goetz. “By replacing the jelly that we used in earlier experiments with this third type of stem cell, we were able to generate structures whose development was astonishingly successful.”

By adding the PESCs, the team was able to see their ‘embryo’ undergo gastrulation, organising itself into the three body layers that all animals have. ̽��ֱ��timing, architecture and patterns of gene activity reflected that of natural embryo development.

Image: Synthetic embryo like structure with embryonic part generated from the embryonic stem cells (pink) and and extra-embryonic tissues in blue. (Credit: Zernicka-Goetz lab, ̽��ֱ�� of Cambridge)

“Our artificial embryos underwent the most important event in life in the culture dish,” adds Professor Zernicka-Goetz. “They are now extremely close to real embryos. To develop further, they would have to implant into the body of the mother or an artificial placenta.”

̽��ֱ��researchers say they should now be in a position to better understand how the three stem cell types interact to enable the embryo to develop, by experimentally altering biological pathways in one cell type and seeing how this affects the behaviour of one, or both, of the other cell types.

“We can also now try to apply this to the equivalent human stem cell types and so study the very earliest events in human embryo development without actually having to use natural human embryos,” says Professor Zernicka-Goetz.

By applying these studies side-by-side, it should be possible to learn a great deal about the fundamental aspects of the first stages of mammalian development. In fact, such comparisons should enable scientists to study events that happen beyond day 14 in human pregnancies, but without using 14-day-old human embryos; UK law permits embryos to be studied in the laboratory only up to this period.

“ ̽��ֱ��early stages of embryo development are when a large proportion of pregnancies are lost and yet it is a stage that we know very little about,” says Professor Zernicka-Goetz. "Now we have a way of simulating embryonic development in the culture dish, so it should be possible to understand exactly what is going on during this remarkable period in an embryo’s life, and why sometimes this process fails.”

̽��ֱ��research was funded by the European Research Council and Wellcome.

Reference
Sozen, B et al. Self-assembly of embryonic and two extra-embryonic stem cell types into gastrulating embryo structures. Nature Cell Biology; 23 Jul 2018; DOI: 10.1038/s41556-018-0147-7

̽��ֱ��creation of artificial embryos has moved a step forward after an international team of researchers used mouse stem cells to produce artificial embryo-like structures capable of ‘gastrulation’, a key step in the life of any embryo.

Our artificial embryos underwent the most important event in life in the culture dish. They are now extremely close to real embryos

Magdalena Zernicka-Goetz

Zernicka-Goetz lab, ̽��ֱ�� of Cambridge

Synthetic embryo-like structure made of three stem cells types in yellow, pink and green

Researcher Profile: Dr Berna Sozen

Dr Berna Sozen is living the dream.

Originally from Turkey, she came to Cambridge to join Professor Magdalena Zernicka-Goetz’s team. “During my MSc, as a young passionate researcher-to-be, I was fascinated by her research, which resolves the puzzles in early mammalian life,” she says. “My dream has come true and I have spent several years at Cambridge now.”

Understanding the very early stages of embryo development is important because it may help explain why a significant number of human pregnancies fail at around the time the embryo implants into the wall of the uterus. Key events after implantation stage of embryo development are largely inaccessible to science because they occur in the ‘black box’ of the human uterus even before most women know that they are pregnant.

̽��ֱ��research is not always easy, of course – her work with Professor Zernicka-Goetz, growing embryo-like structures from mouse stem cells, really is at the cutting-edge of research – but it can be hugely satisfying.

“Observing these self-developing embryo-like structures under the microscope is so exciting that I do not care even if there is a need to be in lab in the middle of night!” she says. “I still clearly remember the moment that I and my co-author saw these structures for the first time. It was a breath-taking moment. Those moments are what we live for in science.”

Berna is helping contribute to the immense legacy that Cambridge has to offer in embryology and stem cell research.

“I work in the same building where Nobel Laureate Bob Edwards succeeded in fertilising a human egg in vitro. Another Nobel Laureate Sir Martin Evans was the first to culture mouse embryonic stem cells and cultivate them in a laboratory at ̽��ֱ�� of Cambridge,” she says. “These works revolutionised treatments for fertility and laid the foundations for human stem cell research. These great scientists paved the way for Magdalena’s pioneering research in embryology. I feel I couldn’t have been in any better place for my research than this.”

̽��ֱ��beautiful images of early embryos produced by Professor Zernicka-Goetz’s team no doubt help inspire Berna’s other passion in life, photography. “Colours and patterns become glamorous behind the lens and I always find the beauty in everything,” she says. “I think this makes me a better biologist!”

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Genome editing reveals role of gene important for human embryo development

sc604 — Wed, 20 Sep 2017 17:00:00 +0000

̽��ֱ��team used genome editing techniques to stop a key gene from producing a protein called OCT4, which normally becomes active in the first few days of human embryo development. After the egg is fertilised, it divides until at about 7 days it forms a ball of around 200 cells called the ‘blastocyst’. ̽��ֱ��study found that human embryos need OCT4 to correctly form a blastocyst.

“We were surprised to see just how crucial this gene is for human embryo development, but we need to continue our work to confirm its role” says Dr Norah Fogarty from the Francis Crick Institute, first author of the study. “Other research methods, including studies in mice, suggested a later and more focussed role for OCT4, so our results highlight the need for human embryo research.”

Dr Kathy Niakan from the Francis Crick Institute, who led the research adds, “One way to find out what a gene does in the developing embryo is to see what happens when it isn’t working. Now we have demonstrated an efficient way of doing this, we hope that other scientists will use it to find out the roles of other genes. If we knew the key genes that embryos need to develop successfully, we could improve IVF treatments and understand some causes of pregnancy failure. It will take many years to achieve such an understanding, our study is just the first step.”

̽��ֱ��research was published in Nature and led by scientists at the Francis Crick Institute, in collaboration with colleagues at Cambridge ̽��ֱ��, Oxford ̽��ֱ��, the Wellcome Trust Sanger Institute, Seoul National ̽��ֱ�� and Bourn Hall Clinic. It was chiefly funded by the UK Medical Research Council, Wellcome and Cancer Research.

̽��ֱ��team spent over a year optimising their techniques using mouse embryos and human embryonic stem cells before starting work on human embryos. To inactivate OCT4, they used an editing technique called CRISPR/Cas9 to change the DNA of 41 human embryos. After seven days, embryo development was stopped and the embryos were analysed.

̽��ֱ��embryos used in the study were donated by couples who had undergone IVF treatment, with frozen embryos remaining in storage; the majority were donated by couples who had completed their family, and wanted their surplus embryos to be used for research. ̽��ֱ��study was done under a research licence and strict regulatory oversight from the Human Fertilisation and Embryology Authority (HFEA), the UK Government's independent regulator overseeing infertility treatment and research.

As well as human embryo development, OCT4 is thought to be important in stem cell biology. ‘Pluripotent’ stem cells can become any other type of cell, and they can be derived from embryos or created from adult cells such as skin cells. Human embryonic stem cells are taken from a part of the developing embryo that has high levels of OCT4.

“We have the technology to create and use pluripotent stem cells, which is undoubtedly a fantastic achievement, but we still don’t understand exactly how these cells work,” explains Dr James Turner, co-author of the study from the Francis Crick Institute. “Learning more about how different genes cause cells to become and remain pluripotent will help us to produce and use stem cells more reliably.”

Sir Paul Nurse, Director of the Francis Crick Institute, says: “This is exciting and important research. ̽��ֱ��study has been carried out with full regulatory oversight and offers new knowledge of the biological processes at work in the first five or six days of a human embryo’s healthy development. Kathy Niakan and colleagues are providing new understanding of the genes responsible for a crucial change when groups of cells in the very early embryo first become organised and set on different paths of development. ̽��ֱ��processes at work in these embryonic cells will be of interest in many areas of stem cell biology and medicine.”

Dr. Kay Elder, study co-author from the Bourn Hall Clinic, says: "Successful IVF treatment is crucially dependent on culture systems that provide an optimal environment for healthy embryo development. Many embryos arrest in culture, or fail to continue developing after implantation; this research will significantly help treatment for infertile couples, by helping us to identify the factors that are essential for ensuring that human embryos can develop into healthy babies.”

Dr Ludovic Vallier, co-author on the study from the Wellcome Trust Sanger Institute and the Wellcome - MRC Cambridge Stem Cell Institute, said: “This study represents an important step in understanding human embryonic development. ̽��ֱ��acquisition of this knowledge will be essential to develop new treatments against developmental disorders and could also help understand adult diseases such as diabetes that may originate during the early stage of life. Thus, this research will open new fields of opportunity for basic and translational applications.”

Reference:
Norah M.E. Fogarty et al. 'Genome editing of OCT4 reveals distinct mechanisms of lineage specification in human and mouse embryos.' Nature (2017). DOI: 10.1038/nature24033.

Adapted from a Francis Crick Institute press release.

Researchers have used genome editing technology to reveal the role of a key gene in human embryos in the first few days of development. This is the first time that genome editing has been used to study gene function in human embryos, which could help scientists to better understand the biology of our early development.

This knowledge will be essential to develop new treatments against developmental disorders and could also help understand adult diseases such as diabetes that may originate during the early stage of life.

Ludovic Vallier

Dr Kathy Niakan/Nature

Day 2 embryo

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

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Human reproduction likely to be more efficient than previously thought

cjb250 — Tue, 13 Jun 2017 10:23:54 +0000

Dr Gavin Jarvis from Cambridge’s Department of Physiology, Development and Neuroscience re-examined data going back to the 1940’s and concluded that previous claims about natural embryo mortality are too often exaggerated. His report is published in F1000Research.

“Trying to determine whether a human embryo survives during the first days after fertilisation is almost impossible,” says Dr Jarvis. “A woman can only suspect that she is pregnant, at the earliest, two weeks after fertilisation, when she misses a period. Using sensitive laboratory tests, embryos can be detected as they implant into the womb about one week after fertilisation. What happens before then under natural circumstances is anyone’s guess.”

In 1938, two doctors in Boston, Dr Arthur Hertig and Dr John Rock, became the first people to see a human embryo when they examined wombs removed from women during surgery. They estimated that a half of human embryos die in the first two weeks after fertilisation. However, Dr Jarvis’s re-analysis of this data shows that this figure is so imprecise as to be of little value.

“I think it is fair to say that their data show that embryos can and do fail at these early stages, and also that many do just fine, but we could say that even without the data,” he adds. “Hertig’s samples, whilst descriptively informative, are quantitatively unhelpful. It doesn’t take us much further than where we would be without the data.”

Pregnancies are also lost after the first two weeks and currently published estimates of total embryo loss from fertilisation through to birth range from less than 50% to 90%. Embryo mortality of 90% implies that only 10% of embryos survive to birth, implying that human reproduction is highly inefficient.

Since 1988, several studies on women trying to get pregnant have provided a more consistent picture. ̽��ֱ��earliest point at which pregnancy can be detected is one week after fertilisation when the embryo starts to implant into the womb of the mother. At this point the hormone hCG, which is used in regular pregnancy tests, becomes detectable. Among implanting embryos, about one in five fail very soon and the woman will have a period at about the expected time, never suspecting that she conceived. Once a period is missed and pregnancy confirmed, about 10-15% will be lost before live birth, mostly within the first few months. In total, once implantation starts, about two thirds of embryos survive to birth. ̽��ֱ��number of embryos that survive and die before implantation remains unknown.

Modern reproductive technologies have enabled fertilisation to be observed directly in the laboratory. Poor survival of in vitro embryos may have contributed to the pessimistic view about natural human embryo survival, says Dr Jarvis.

“Fertilising human eggs and culturing human embryos in the laboratory is not easy. A large proportion of eggs fertilised in vitro do not develop properly even for a week. Of those that do and are transferred into women undergoing IVF treatment, most do not become a new-born baby.”

This failure of in vitro embryos may reflect the natural situation. Alternatively, the artificial environment of reproductive treatments may contribute to the high failure rate of IVF embryos. Dr Jarvis’s re-analysis of the data suggests that the latter is the case.

“It’s impossible to give a precise figure for how many embryos survive in the first week but in normal healthy women, it probably lies somewhere between 60-90%. This wide range reflects the lack of relevant data. Although we can’t be precise, we can avoid exaggeration, and from reviewing the studies that do exist, it is clear that many more survive than is often claimed,” concludes Dr Jarvis.

Reference
Gavin E Jarvis. Early embryo mortality in natural human reproduction: What the data say. f1000research; DATE; DOI: 10.12688/f1000research.8937.2

Gavin E Jarvis. Estimating limits for natural human embryo mortality. f1000research; DATE; DOI: 10.12688/f1000research.9479.2

How difficult is it to conceive? According to a widely-held view, fewer than one in three embryos make it to term, but a new study from a researcher at the ̽��ֱ�� of Cambridge suggests that human embryos are not as susceptible to dying in the first weeks after fertilisation as often claimed.

It’s impossible to give a precise figure for how many embryos survive in the first week but in normal healthy women, it probably lies somewhere between 60-90%

Gavin Jarvis

Esparta Palma

Dos rayitas

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