Artificial sperm is available, male infertility can also give birth to a baby?

Release date: 2015-12-21

For the past 20 years, scientists have been trying to cultivate "artificial sperm cells" in the laboratory. For the results of this research, the British "Independent" said that this news caused a sensation in the medical community, but many Western media are cautious about new results, saying that this major "medical breakthrough" still needs to be verified.

　　 Text / Reporter Qi Yafeng Editor / Sun Yanyan

Artificial sperm for a 72-day journey

Kallistem CEO said in an interview: "Kallistem is working to solve the major problems affecting countries around the world: male infertility treatment. Our team developed the world's first technology to allow fully formed sperm in vitro."

Kallistem was founded in 2012 and the team members are basically Ph.D. in biology. It took them 15 years to slowly turn the immature cells into mature sperm.

In fact, the technique of sperm production is quite complicated. In order to improve the technology to improve sperm production, this method involves extracting the suspension in the seminiferous tubule, which is a gel called chitin. Place the extract in a petri dish rich in nutrients, vitamins, hormones and growth factors and place the dish in the bioreactor. Kallistem researchers claim that the sperm production process takes 72 days to complete in the human body until it leaves the seminiferous tubules, the gel dissolves, and the sperm matures.

Previously, they only did this experiment on mice, and now they are successful in human cells for the first time. If they are successful, they will complete the pre-clinical experiment 1 year later. If the experiment is successful, then in 2017 they can use clinical trials to give infertile patients a child. They will remove the immature spermatogonia from the male testicles, then convert the genetic material to form mature sperm and use the test tube to make the baby. If the patient is not planning to be a dad, he can choose to freeze the sperm first.

Research teams from Japan have successfully created mouse sperm cells in the laboratory as early as 2011, but French researchers have emphasized that they are the first countries in the world to conduct human experiments. The company's official website also details the steps to make "artificial sperm." This process is divided into five steps. First, testicular tissue puncture is performed on boys and adult males who are infertile due to testicular cancer or other causes, and stem cells are extracted. Then, the stem cells are cryopreserved, and the germ cells are cultured into mature sperm cells in a culture dish; in the third step, the mature sperm cells are cryopreserved in a "bioreactor" simulating the human environment; the fourth step, Inject sperm into the body from outside; the fifth step, pregnancy.

The process of "artificial sperm" sounds very "high" and difficult to understand. Is spermicidal cell cultured from spermatogonia, is this technique feasible? Dr. Xia Zhi, a professor of biology in the United States, told reporters that "cultivating spermatogonia cells into sperm cells is not a big problem. Sperm cells are produced by spermatogonia and meiosis. Semen cells belong to male germ cells. The early stage. The cultivation of sperm cells by spermatogonia is the artificialization of this process in nature. It is a scientific manifestation of the early process of manipulating natural life and is a technological advancement."

If the trial is successful, the company hopes that artificial sperm can help young men with cancer of the reproductive system become fathers, simply the gospel of infertility patients. The company said on the official website that the technology will be applied to 15,000 young cancer patients, or 120,000 adult infertile men, who cannot solve the problem of infertility through the existing IVF technology. Breakthrough has opened up a new path, which is a long-awaited treatment path for clinicians."

The human body verification effect still takes several years

Seeing this, many male compatriots may breathe a sigh of relief, because the spermatogonia in the French study is still provided by men, and it is cultivated into sperm cells.

So, is sperm cell and sperm the same thing? Can sperm cells be cultivated into mature sperm? Xia Zhi said, "Sperm cells and sperm are not the same. Sperm cells are the early stages of sperm, but also through deformation, such as acrosome formation, tail development, cytoplasmic condensation and other processes. The understanding of this process and the specific mechanism is not deep enough, It is one of the main reasons for the problems of sperm formation and the high success rate, and the subsequent survival of the offspring is low."

The study was successful in mice, so if the test is usually successful on animals, can it be successfully used on the human body? What stage do you have to go through? “The transition from animal experiments to the human body is an extremely long process. At this point, the public and various news reports are very likely to confuse the two boundaries. It will feel that 'animals can be, can people still be far behind? 'It’s not right to treat the two as equivalent.” Xia Zhi explained, “Human as an extremely complex higher animal, its life mechanism and physiological regulation process are very different from other animals, and more complicated and easier. Caused by major adverse consequences and effects. Generally speaking, it is a model animal experiment. The common ones are mice, zebrafish, and then transition to animals that are relatively close to humans, such as dogs, pigs, monkeys, and finally start again. Perform one or two trials on the human body to verify and explore its effects, and its possible adverse reactions."

In fact, this technology is also of great value for animal protection. Today, when large wild animals are increasingly scarce, this technology can effectively make some rare female animals lack male individuals, or male individuals have serious sperm quality. When descending, sperm remodeling experiments are carried out to allow female individuals to conceive and multiply and continue the number of species.

Global research on fertility sperm

In the long run, researchers have spent huge sums of money on this seemingly meaningful study. However, although the company is confident in its own results, the academic community still questioned this achievement. In recent years, research on artificial sperm has shown a new development of similar research at regular intervals, but the final research results are endless.

In 2010, the British "Daily Mail" reported that British scientists wanted to extract stem cells from the bone marrow of female donors and then use special chemicals to turn them into sperm. This seems to mean that women can also produce “artificial sperm” in disguise, making men completely redundant. Although the study was full of confidence at the time of publication, it said that "female sperm" will be available within two years, but five years have passed, and this result has not been released to the outside world.

In a study published in the journal Nature in February 2011, researchers led by reproductive biologist Takehiko Ogawa of Yokohama City University in Japan removed the testes of young rats born two or three days and placed the testes One contains a dedicated medium. The researchers then allowed the testicles to grow. About a month later, the researchers noticed that the testes looked quite normal and were producing sperm. The researchers extracted sperm and artificially invigorated the female, when the pregnant female had produced 12 healthy mice. Using the same method, the researchers were able to produce sperm from young testes that had been frozen for 1 month. Experts at the time believed that this technology was important for the treatment of male sterility.

According to the British "Daily Telegraph" website, on January 3, 2012, German and Israeli researchers extracted germ cells that control sperm production from mouse testis and placed them in a special compound composed of agarose gel. In order to create an environment similar to the growth of sperm in the testis, we finally succeeded in breeding healthy sperm with fertility. At the time, they believed that this technology could one day help a man with no reproductive ability to achieve a "father dream."

China's artificial sperm cell technology is at the forefront

It is worth mentioning that the incredible fact of human beings is that while our reproductive technology is constantly improving, the quality of male sperm around the world is generally declining. There are data showing that infertile couples in the United States are around 10%-15%. This ratio is higher in the UK. About 1 in 6 couples have problems with fertility. How is China doing in this regard?

October 28th is Male Health Day every year. According to the relevant literature and data released by the 2015 National Men's Annual Meeting, the qualified rate of Shanghai volunteers donated no more than 21%, Henan sperm bank donation rate is 22%, Beijing qualified donors only 15%, Chinese male sperm The quality drops by more than 1% per year, the number is reduced by 30%, and at least 10 out of every 100 couples are infertile...

China is also at the forefront of the world in the field of artificial sperm cell research. On July 10, 2015, the research team of Li Jinsong, a researcher from the Shanghai Institute of Biological Sciences of the Chinese Academy of Sciences, successfully established a stable "sperm cell-like" haploid cell line, which was cloned from the somatic cells of young male rats. "Sperm-like sperm" can stably bind to the egg cells of female mice to produce semi-cloned mice. Related research is published in the authoritative academic journal Cell Stem Cell. Because of the great role and reference value of mouse research in human health and cancer research, these semi-clonal mice with stable inheritance are of great significance.

For experimental animals, 20% of healthy offspring may be good enough, but not in humans," said Researcher Li Jinsong. "If the technology is used on human sperm, it will cause 80% of deaths or deaths at birth. defect. ”

As early as 2012, the Li Jinsong team claimed to put a sperm into an egg cell that had removed the nucleus and genetic material. As a result, the experiment obtained a stem cell similar to an embryonic cell, which has a sperm-like function but no tail and cannot swim. This stem cell can be used to generate similar artificial cells in large quantities. However, the current efficiency of the technology is still very low, and the fertilized eggs obtained can only produce 20% of healthy offspring.

Li Jinsong also mentioned that the technology can provide an effective way to make genetically modified animals, thus helping the research of diseases in the laboratory.

Ethical conventions will still be challenged

Despite the wide-ranging medical needs of “artificial sperm”, research on “artificial sperm” has also led to ethical discussions. This French study has produced sperm cells from male spermatogonia, and it seems that the ethical issues are not too big. Xia Zhi said, "But if you secretly get someone's spermatogonium, you don't need to steal the sperm or normal sex life, you can fertilize it silently and cultivate a lot of offspring. At this time, safety and ethics. Regularity will also be challenged."

At present, unlike the French research technique, foreign related research mentions that stem cells can be cultivated into sperm cells in a laboratory environment. Stem cells are transdifferentiated into sperm cells in different laboratories around the world. The techniques are different. Some use spermatozoa, some use compounds or small molecules, and some use new gene editing techniques.

In a study published in the journal Cell on December 24, 2014, scientists not only induced skin cells completely into inducible stem cells (iPS) in vitro, but also differentiated them into human primordial germ cells (hPGCLC). The first step in building human sperm and eggs.

　　 Jiang Yan, a senior engineer at the Institute of Genetics and Development of the Chinese Academy of Sciences, said that the Cali plant is in vitro culture of primordial germ cells, which is quite different from the differentiation of dermal skin cells into primordial germ cells published in 2014. There is a big difference in ethics. This time, germ cells are cultured in vitro. The methods of acquisition, culture, and artificial insemination are in line with international conventions. "To put it bluntly, the artificial insemination technique has been carried out in stages. Move, let those men who can not produce sperm have the possibility of nurturing their next generation, because the extracted spermatogonia is the predecessor of sperm, it can be said that this technology is to perfect the IVF technology."

In addition, Jiang Yan added a point: the in vitro culture of germline stem cells to make patients conceived is a technological advancement, but it should also be considered whether the genes for infertility will be passed on to the next generation after conception. The next generation still retains this gene, so the entire community will always need to rely on the support of technology to multiply. "This requires further thinking from the perspective of humanitarian care, whether it requires the intervention of genetic editing technology, the gene of infertility. Knock-out? Whether gene editing technology itself can achieve this expectation depends on the power of science and technology, and it is still to be discussed from an ethical perspective."

Perhaps, with the advancement of science and technology, there is no need for men, not even women, and it is possible to have children. In fact, the most terrible thing is that if a day can completely divert skin cells into germ cells, then it is troublesome, and there will be many ethical issues. It is conceivable that if at that time, for example, the woman likes someone, she does not need to have sex with the man, and only by getting the man's skin cells (very easy to get), he can give birth to a child. "Of course, there are already conventions in the international arena. Any reproductive technology with ethical ethics cannot be used for the transformation of human embryos, so it is not necessary for men's fertility to be allowed at this stage," Jiang said.

At present, it is also puzzling that the quality of sperm that is artificially cultivated in the future will be exactly the same as that produced by ordinary males. Xia Zhi explained, "Artificial is not the same as nature, unless we clear its 100% research. Artificial simulation of natural objects, natural processes are the inevitable process of human exploration of the world and scientific research. I believe that as we study Intensively, the quality of artificial sperm will be infinitely similar to the naturally produced sperm, and even better from a certain perspective."

Source: Qi Yafeng

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