For the first time ever, scientists at Oxford University have managed to have a look at a human embryo that is between 14 and 21 days after fertilization. We’ve actually never been able to observe an embryo at this mysterious stage because after fertilization in processes like IVF or just in lab cultures, the embryo is allowed to be cultured only for about 14 days before getting transplanted into the womb.
When women terminate pregnancies and donate embryos to research, it is typically after 12 weeks from fertilization because until that point, not many people even realize that they’re pregnant.
After Fertilization
In this article, we’ll take a look at what the researchers found in this embryo that was aged about 16 to 19 days after fertilization, the different cells that they discovered this embryo had, which systems had developed in the embryo and how these findings compared to animal models and experimental models that we’ve been using so far.
When a human embryo is about three weeks after fertilization, the basic blueprint of the body is laid out. This happens between 14 and 21 days and the process is called gastrulation. Gastrulation is a very fundamental biological process and it occurs in all multicellular animals. In humans, it occurs about a week after the embryo implants into the wall of the uterus. We’ve never studied or analyzed a human embryo at this stage and most of what we think happens at this stage comes from animal models involving mice and non-human primates, experimental models and in vitro cultured samples or lab samples that are allowed to exist only for 14 days in the lab. When an embryo begins to form, it is made up of stem cells.
What are Stem Cells?
Stem cells are cells that are unspecialized but have the ability to develop into any other specialized human cell. They can go on to become muscle cells or blood cells or brain cells or literally any other cell in the body. Such cells are said to be pluripotent which means they have the power to transform to any other cell.
When gastrulation occurs, these stem cells start to take on new functionality and assume their final role in the body. Gastrulation is also when some genes start to express themselves or get turned on. There is a huge and sudden diversification of cells and different cell types and then similar cells start to cluster together.
We need to really be able to understand what happens during gastrulation because human pregnancy is actually not biologically very efficient. Nearly a third of all fertilization is miscarried and the embryo is lost before the embryo implants into the wall of the uterus. And even after implantation, about a fifth of pregnancies result in miscarriage mostly from chromosomal defects in the embryo which prevent it from surviving.
Miscarriage in humans is surprisingly more common than most of us think it is. And that’s all the knowledge that we have. We don’t understand how the embryo which forms from just a single cell undergoes this cell diversification and at which stage.
- When do we develop red blood cells?
- When do we develop white blood cells?
- When do we develop brain cells?
- When do we develop a heart?
- When do we develop a nervous system?
Questions like these are what the researchers set about trying to answer when they analyzed this embryo. The embryo that they received for research was donated voluntarily and with informed consent from a donor who was terminating her pregnancy. Typically, at this stage most women cannot tell that they are pregnant but this person was able to.
The embryo was male and did not have any chromosomal defects. The team which was led by Oxford dissected the sample of the embryo and then sequenced it. The process they used was called single cell RNA sequencing.
It is exactly as it sounds. The RNA or mRNA from individual cells was taken and sequenced and the sequencing is done just like it’s done for COVID for the virus. The mRNA was isolated and then amplified through 21 PCR cycles.
What is PCR?
PCR is polymerase chain reaction and it amplifies the RNA. This amplification enables scientists to get some substantial quantity of material to work with and study. So, when the researchers analyzed and examined this embryo, they discovered that at this stage the embryo structurally has two parts or two cavities.
The amniotic cavity and the yolk sac which is separated by a disc of embryonic material.
In the embryo there were a total of 1195 cells only and the researchers looked into each of these to see which genes were active. The findings showed that what we know from mice and monkeys are actually quite similar to what happens in human embryos with some differences.
The first discovery that they made was that there were primordial germ cells in the embryo. Germ cells are one of two fundamental types of cells in our body the other being somatic cells. Germ cells or germline cells produce gametes or sex cells.
They undergo both mitosis and meiosis and are engaged in sexual reproduction. Somatic cells are just any cells that are not sex cells so every other kind of cell in the body. Those undergo only mitosis. So at this very early-stage, early versions of sex cells develop which eventually go on to become either egg cells or sperm cells. This actually we’ve seen before in the lab and it tends to occur at about 11 days after fertilization when the sex of the embryo can be determined. Analyzing different clusters of cells showed that even primordial blood cells which go on to become red blood cells and white blood cells start to develop at this stage.
But the most important finding that the researchers made was that there was no evidence of anything that would go on to become nerve cells, nerve tissues or anything that would resemble cells belonging to the nervous system. This means that there is no sensation in the embryo at this stage and the nervous system formation occurs much later. These findings are very important for research and they are very unique even though only one embryo was studied so far.
A leading center of excellence, Medline Academics is committed to improving education in related sciences and reproductive medicine (best IVF fellowship in India). It provides a wide range of online and offline courses, interactive seminars, and practical training programs with an emphasis on information exchange and skill development. For gynaecologists, embryologists, andrologists, medical students, science graduates, and paramedical workers, these programs provide worthwhile educational possibilities. Medline Academics, which was founded under the direction of Padma Shri Prof. Dr. Kamini A Rao and top authorities on assisted reproductive technologies and infertility, combines evidence-based education with practical clinical application to close the knowledge gap between theory and practice. Its goal is to teach people in IVF and Fellowship in Embryology so they can offer exceptional patient care and help shape the direction of reproductive healthcare in the future.
Extremely conservative ethical guidelines around the world have put an upper limit on growing embryos in the lab human embryos and this limit is capped at 14 days. Countries that are very rigid culturally about abortion and terminating pregnancies like the US and even the UK have actually turned this limit into law. The researchers were able to work with this embryo because it was not grown in the lab and it was donated voluntarily with consent after termination of a pregnancy.
This has been a subject of debate for a while whether to increase this 14-day limit or if it is appropriate. But now from this discovery we can tell that the lack of nervous cells in an embryo at this stage means that the embryo cannot feel pain. In fact, it cannot feel anything much at all. So, these findings are now a big push to increase this limit so that we can study embryos in more detail in the lab and understand how human growth occurs. Studying embryos at this stage helps us understand the difference between human models and animal models, mice models and non-human primate models. For example, mice already tend to develop a nervous system at this point but clearly humans do not. So, while mice models are a very good representation for human systems, they are not 100% accurate and cannot be relied upon entirely. These findings are a huge leap in the of embryology with many other scientists and biologists calling these landmark findings. Understanding gastrulation helps us understand things like genetic defects and neural tube defects that could potentially save hundreds of thousands of lives in the future.
Understanding how stem cells develop into specialized cells will provide breakthroughs in stem cell research and regenerative medicine. All in all, the findings present a very strong case for further investigation into human embryos in the lab and revision of the 14-day limit.
Dr. Kamini Rao Hospitals – The Clinical Partner
As part of our IVF Fellowship Program, we offer our mentees the chance to observe and gain hands-on experience in real patient cases at Dr. Kamini Rao Hospitals, which is home to some of the leading IVF Center in Bangalore. In addition to offering IVF treatments, the hospitals also provide other advanced procedures such as frozen embryo transfer and intracytoplasmic sperm injection (ICSI). Our approach to treating infertility is comprehensive, addressing both the emotional and physical aspects of the condition to ensure the best possible care for our patients.
Continuing medical education (CME) plays a vital role in ensuring that healthcare professionals maintain their qualifications, stay updated with the latest medical advancements, and consistently improve their clinical expertise. This hospital is not just about meeting basic requirements or following rules; it’s about enhancing one’s professional growth and delivering the highest quality of care to patients. This ongoing learning process helps professionals stay at the forefront of their field, ultimately benefiting both the medical community and the individuals they serve.
