Building a new mouse, one stem cell at a time

Science is full of acronyms. There are days where it feels like you need a decoder ring just to understand a simple sentence. A recent study found that between 1950 and 2019 researchers used more than 1.1 million unique acronyms in scientific papers. There’s even an acronym for three letter acronyms. It’s TLAs. Which of course has one more letter than the thing it stands for.

I only mention this because I just learned a new acronym, but this one could help change the way we are able to study causes of infertility. The acronym is IVG or in vitro gametogenesis and it could enable scientists to create both sperm and egg, from stem cells, and grow them in the lab. And now scientists in Japan have done just that and allowed these fertilized eggs to then develop into mice.

The study, published in the journal Science, was led by Dr. Katsuhiko Hayashi of Kyushu University in Japan. Dr. Hayashi is something of a pioneer in the field of IVG. In the past his team were the first to produce both mouse sperm, and mouse eggs from stem cells. But they ran into a big obstacle when they tried to get the eggs to develop to a point where they were ready to be fertilized.

Over the last five years they have worked to find a way around this obstacle and, using mouse embryonic stem cells, they developed a process to help these stem cell-generated eggs mature to the point where they were viable.

In an article in STAT News Richard Anderson, Chair of Clinical Reproductive Science at the University of Edinburgh, said this was a huge achievement: “It’s a very serious piece of work. This group has done a lot of impressive things leading up to this, but this latest paper really completes the in vitro gametogenesis story by doing it in a completely stem-cell-derived way.”

The technique could prove invaluable in helping study infertility in people and, theoretically, could one day lead to women struggling with infertility to be able to use their own stem cells to create eggs or men their own sperm. However, the researchers say that even if that does become possible it’s likely a decade or more away.

While the study is encouraging on a scientific level, it’s raising some concerns on an ethical level. Should there be limits on how many of these manufactured embryos that a couple can create? Can someone create dozens or hundreds of these embryos and then sift through them, using genetic screening tools, to find the ones that have the most desirable traits?

One thing is clear, while the science is evolving, bioethicists, scholars and the public need to be discussing the implications for this work, and what kinds of restraints, if any, need to be applied before it’s RFPT (ready for prime time – OK, I made that one up.)

Eggciting News: Scientists developed fertilized eggs from mouse stem cells

A really eggciting science story came out early this week that’s received a lot of attention. Scientists in Japan reported in the journal Nature that they’ve generated egg cells from mouse stem cells, and these eggs could be fertilized and developed into living, breathing mice.

This is the first time that scientists have reported the successful development of egg cells in the lab outside of an animal. Many implications emerge from this research like gaining a better understanding of human development, generating egg cells from other types of mammals and even helping infertile women become pregnant.

Making eggs from pluripotent stem cells

The egg cells, also known as oocytes, were generated from mouse embryonic stem cells and induced pluripotent stem cells derived from mouse skin cells in a culture dish. Both stem cell types are pluripotent, meaning that they can generate almost any cell type in the human body.

After generating the egg cells, the scientists fertilized the eggs through in vitro fertilization (IVF) using sperm from a healthy male mouse. They allowed the fertilized eggs to grow into two cell embryos which they then transplanted into female mice. 11 out of 316 embryos (or 3.5%) produced offspring, which were then able to reproduce after they matured into adults.

mice

These mice were born from artificial eggs that were made from stem cells in a dish. (K. Hayashi, Kyushu University)

Not perfect science

While impressive, this study did identify major issues with its egg-making technique. First, less than 5% of the embryos made from the stem-cell derived eggs developed into viable mice. Second, the scientists discovered that some of their lab-grown eggs (~18%) had abnormal numbers of chromosomes – an event that can prevent an embryo from developing or can cause genetic disorders in offspring.

Lastly, to generate mature egg cells, the scientists had to add cells taken from mouse embryos in pregnant mice to the culture dish. These outside cells acted as a support environment that helped the egg cells mature and were essential for their development. The scientists are working around this issue by developing artificial reagents that could hopefully replace the need for these cells.

Egg cells made from embryonic stem cells in a dish. (K. Hayashi, Kyushu University)

Egg cells made from embryonic stem cells in a dish. (K. Hayashi, Kyushu University)

Will human eggs be next?

A big discovery such as this one immediately raises ethical questions and concerns about whether scientists will attempt to generate artificial human egg cells in a dish. Such technology would be extremely valuable to women who do not have eggs or have problems getting pregnant. However, in the wrong hands, a lot could go wrong with this technology including the creation of genetically abnormal embryos.

In a Nature news release, Azim Surani who is well known in this area of research, said that these ethical issues should be discussed now and include the general public. “This is the right time to involve the wider public in these discussions, long before and in case the procedure becomes feasible in humans.”

In an interview with Phys.org , James Adjaye, another expert from Heinrich Heine University in Germany, raised the point that even if we did generate artificial human eggs, “the final and ultimate test for fully functional human ‘eggs in a dish’ would be the fertilization using IVF, which is also ethically not allowed.”

Looking forward, senior author on the Nature study, Katsuhiko Hayashi, predicted that in a decade, lab-grown “oocyte-like” human eggs will be available but probably not at a scale for fertility treatments. Because of the technical issues his study revealed, he commented, “It is too preliminary to use artificial oocytes in the clinic.”