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Japanese scientists "litter" with two male mice? This is not the whole truth

author:Engineer Tian Zhang

From time to time, we are attracted by news such as "daddy is pregnant", and when we open it, it is not like that at all. This time Japanese scientists used two male mice to "give birth", do you think it will be true? After reading it, I found that this is news that only gives part of the facts.

Too long to look at the version

The research path of scientists this time is: male mouse skin cells (2) are → respectively remove the Y chromosome→ the remaining 2 X chromosomes are "glued" together→ cultivated into mature egg cells→ another male mouse sperm is introduced to impregnate egg cells→ implanted into the female mouse uterus→ mice give birth.

In fact, the breeding process does not only need two male rats, but this research also has many original and first-of-its-kind places, and the research process is not all smooth sailing, if you are interested, please continue to read.

How rats normally reproduce

Like humans, mice contain XY chromosomes in male germ cells and XX chromosomes in female germ cells, and male offspring are produced if the XX chromosomes of the parents are combined, and male offspring are produced if the X chromosome of the mother mouse is combined with the Y chromosome of the male mouse. After conception, the fertilized egg matures in the female mouse uterus for a short time (about 1 month) and is delivered.

Japanese scientists "litter" with two male mice? This is not the whole truth

The first attempt by Japanese scientists

Dr. Katsuhiko Hayashi of Kyushu University in Fukuoka, Japan, has been working to understand the molecular mechanisms of mouse germ cell specification and differentiation. He has been a professor at the Department of Stem Cell Biology and Medicine at Kyushu University since 2014. In 2004, he received his Ph.D. from Tokyo University of Science and joined the laboratory of Yasuhisa Matsui at Osaka Women's and Children's Hospital. In 2005, he joined Azim Surani's lab at the University of Cambridge as a postdoctoral researcher. In 2009, he joined the lab of Mitinori Saitou at Kyoto University.

Japanese scientists "litter" with two male mice? This is not the whole truth

Dr. Shengyan Hayashi and his team will do something big to abandon the traditional normal mouse pregnancy mechanism, and instead try to create germ cells (sperm and eggs) from mouse stem cells and grow them in the laboratory. This field was called IVG, or in vitro gametogenesis, and he became a pioneer in the field of IVG. A so-called stem cell is a type of cell that can be transformed into other types of cells.

How did they do it? In 2012, while at Kyoto University, Lin teamed up with stem cell biologist Mitinori Saitou to study ways to "make" mouse skin cells into eggs: reprogramming them into embryo-like stem cells and then reediting them into primordial germ cells (PGCs). These early cells emerge as the embryo develops and later produces sperm or eggs.

Japanese scientists "litter" with two male mice? This is not the whole truth

The 11-month-old mice developed from eggs made by Lin's team in petri dishes

Later, Lin Shengyan's team became the first team in the world to produce mouse sperm and mouse eggs from stem cells, and it was also the first time to artificially manufacture mouse eggs in vitro in female mice. This is already a remarkable achievement, they think: if the process can work for humans, researchers can produce artificial eggs.

It's not easy, but they don't stop there, and as they continue to try to get the eggs to the point where they are ready for fertilization, they run into a big hurdle – they can't mature outside the body. To mature these extracorporeal "made" eggs, the researchers had to transfer them into the ovaries of living mice.

Japanese scientists "litter" with two male mice? This is not the whole truth

Egg cells in a dish: artificial mouse oocytes produced from embryonic stem cells. The researchers also reprogrammed the skin cells' eggs into an embryo-like state

Continued attempts by Japanese scientists

From then on, until 2021, for five years, Lin's team has been trying to find a way around this hurdle, so they developed a process to help the eggs produced by these stem cells mature to a feasible level. In 2020, they studied the genetic changes required for mouse stem cells to mature into eggs in a laboratory dish; In 2021, they demonstrated that the environment of mouse ovaries could be reconstructed to produce eggs that produced healthy offspring. This time they succeeded, how did they do it?

Japanese scientists "litter" with two male mice? This is not the whole truth

In the first step, skin cells with XY chromosomes were removed from adult male mice;

In the second step, the cells were reprogrammed to create stem-like induced pluripotent stem cells, which were cultured in culture until they spontaneously lost the Y chromosome, leaving only one X chromosome;

In the third step, the X chromosome is left in another cell that also culled the Y chromosome, and "sticks" with the previous X chromosome, in this process they treat the cells with a compound called reversal, promote the error of chromosome distribution during cell division, and look for cells with female chromosomes, which have two copies of the X chromosome; From there, the team provided induced pluripotent stem cells with the genetic signals needed to form immature eggs, which gradually mature in a petri dish to a state where they could be fertilized;

In the fourth step, the eggs are fertilized using mouse sperm and the resulting embryos are transferred to the uterus of the female mouse.

After a large number of trials, only 7 of the 630 transferred embryos developed into pups. Lin's team found that the survival rate of this practice was very low, about 1%, but the good news was that the pups grew normally and became fertile as adults.

epilogue

Lin Shengyan's team first used a male rat skin cell to eventually grow into a mature egg, then used the sperm of another male mouse to impregnate the cultured egg, and finally borrowed the body of a female mouse to mature and deliver it. In this way, the birth of a mouse does have two fathers, and the mother mouse only provides a place for development, and there is no parental relationship between the mouse and the female mouse.

Japanese scientists "litter" with two male mice? This is not the whole truth

What is the use of this research? This technology could be invaluable in helping to study human infertility. Theoretically, one day it could lead to women battling infertility and being able to use their own stem cells to make eggs or a man's own sperm. The technique can be used to help infertile couples whose women are unable to produce eggs on their own.

But from an ethical point of view, Lin Shengyan does not approve of men using this technique to create babies with their own sperm and artificially created eggs. One is that there are many problems with the quality of eggs even in mice, and the other is that fertility treatment is still a long way from being available. Experts in the same industry say that technically it is possible, but it is not certain that this technology is safe or socially acceptable at this stage.

#所见所得, very scientific ## headline creation challenge ##头条小组红人扶持计划 #

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