Nature: A nearly perfect human blastocyst model was born, and women are expected to have reproductive rights

Reproduction has been one of the most important life processes of human beings since ancient times. However, even in modern society with relatively advanced medical technology, it is still difficult for humans, especially women, to control their own fertility.

For example, if we don’t want to be disturbed by condoms, don’t want to suffer the side effects of hormonal emergency contraceptives, don’t want to take short-acting contraceptives for a long time, and don’t want to get pregnant, how can we happily "applaud for love"?

Similarly, if we don’t want to repeatedly try the painful process of IVF “ovulation-egg retrieval-fertilization-embryo transfer”, but still want to have a child, how can we improve the success rate of IVF?

Recently, a research team led by Dr. Nicolas Rivron from the Institute of Molecular Biotechnology of the Austrian Academy of Sciences identified three new signaling pathways that can be used to use human stem cells to construct a "perfect" human in vitro embryo model comparable to real human blastocysts.

At the same time, using this model, the researchers found the key factors in early human embryo implantation and blastocyst formation, laying the foundation for the development of new non-hormonal, female-friendly contraceptive drugs and improving the success rate of in vitro fertilization.

In this regard, Dr. Rivron said, "The establishment of a human embryo model can better replace human embryo research and resolve the conflict between biomedical issues and human ethical issues. Our goal is to empower women through early human embryo model research so that women can better control their fertility, whether they want to avoid pregnancy or become pregnant."

The study, titled "Human blastoids model blastocyst development and implantation," was published in the recent journal Nature.

What is a human blastocyst model?

We all know that human life begins with the fertilized egg formed by the combination of the father's sperm and the mother's egg. Subsequently, the fertilized egg cell moves toward the uterus while dividing. When it reaches the appropriate part of the uterus, it has evolved into a blastocyst composed of the trophoblast, epiblast and hypoblast. After the blastocyst implants, that is, after being "closely" connected with the mother's cells, the trophoblast, epiblast and hypoblast develop into the placenta, embryo and yolk sac respectively...

However, with the development of life sciences to this day, scientists still have very limited understanding of the early human embryonic development process, such as the formation and development process of the early blastocyst, the specific mechanism of blastocyst implantation, etc.

(Source: Pixabay)

One important reason for this situation is that using real human embryos for biological research will bring about a series of ethical issues. After all, a real human embryo is also a small life.

Obviously, in order to reveal the origin of human life and understand the secrets of human embryonic development, scientists must find other alternative methods. In vitro stem cell culture is one of the important directions. Unfortunately, although several research teams have successfully used mouse stem cells to build mouse blastocyst models in vitro, scientists are still struggling in the model research of human blastocyst-like structures.

Until March 17, 2021, Nature magazine reported two breakthroughs. The team of Professor Wu Jun from the Texas Southwestern Medical Research Center and the team of Professor Jose Polo from Monash University in Australia successfully obtained blastocyst models of the earliest development stage of human embryos using human pluripotent stem cell induction and adult cell reprogramming technology. Both blastocyst-like structures contain the stem cell types in real human blastocysts, with consistent spatial distribution, and can simulate the development and implantation process of early human embryos in a laboratory environment.

These two studies perfectly integrate the scattered information of human embryos and construct an experimental model with potential application value for scientists to understand the earliest development of embryos. The importance of this model is self-evident.

(Source: pixabay)

However, in the above two articles, the researchers also mentioned that the research has certain limitations. For example, the induction efficiency of blastocyst-like structures is low and the acquisition rate is not stable enough; the results of single-cell transcriptome analysis suggest that blastocyst-like structures also contain some cell types that do not exist in real blastocysts.

That said, these models are not perfect.

A more perfect human blastocyst model

In the above two studies, although the two research teams used different methods to successfully construct human blastocyst models, these methods were not perfect, with a success rate of only 20%, and there were still differences between the constructed blastocysts and real human blastocysts.

To solve these problems, the research team led by Dr. Rivron conducted research on human pluripotent stem cells and found that when the three classic signaling pathways of Hippo, TGF-β and ERK were inhibited, human pluripotent stem cells could "perfectly" simulate the development process of normal human blastocysts, with a success rate of over 70%. At the same time, the blastocyst model formed by this method is more than 97% similar to the cells in normal human blastocysts.

Figure | Human blastocyst model (Source: Nature)

During the in vitro culture process, the researchers found that these human blastocyst models can well simulate the normal human embryonic development process, which is almost the same as the normal human embryonic development process. This means that this human blastocyst model can provide a real and reliable method for studying the early human embryonic development.

In subsequent studies, using these human blastocyst models, Dr. Rivron found that SC144, an FDA-approved oral small molecule gp130 inhibitor, can effectively inhibit the implantation process of human blastocyst models in simulating the normal implantation process of human embryos. This has also opened up a new direction for the research and development of a new generation of non-hormonal contraceptives for humans.

After all, both emergency contraceptive pills and short-acting contraceptive pills taken daily have certain side effects, and once short-acting contraceptive pills are missed, the contraceptive effect will be greatly reduced. In contrast, this type of new contraceptive only needs to be taken when necessary, eliminating the pressure of taking medicine every day and avoiding the adverse reactions of hormonal drugs, making contraception easier, more convenient, and more in line with human needs.

Figure | Fluorescently labeled human blastocyst cells (Source: Nature)

Similarly, in addition to contraception, Dr. Rivron and his team also discovered in the process of studying the human blastocyst model that a naturally occurring small molecule LPA in the human body can greatly improve the self-organization of stem cells, effectively promote the formation of natural embryos during in vitro fertilization, and improve the success rate of in vitro fertilization, which is of great significance for in vitro fertilization technology.

It is reported that Professor Hilde Van de Velde of the Free University of Brussels in Belgium is currently applying to add LPA molecules to the in vitro fertilization design process to improve the success rate.

In general, Dr. Rivron and his team used a new technology to successfully transform human pluripotent stem cells into a human blastocyst model, which is very similar to a normal human blastocyst, and can simulate the early development of human embryos in vitro and avoid some ethical issues. At the same time, the researchers discovered two molecules during the experiment, which also paved the way for improving the success rate of human in vitro fertilization and developing new non-hormonal contraceptive methods.

References:

https://www.nature.com/articles/s41586-021-04267-8

https://www.oeaw.ac.at/imba/research-highlights/news/breakthrough-research-on-human-blastoids-and-impact-on-ivf-and-contraception

Written by: Zhu Hengheng Edited by: Wang Haha Layout by: Li Xuewei

Source: Academic Headlines