Scientists managed to reprogram stem cells into spermatozoon precursor cells

Scientists have long been trying to get sperm and eggs in the laboratory. This would allow us not only to understand more deeply one of the most fundamental biological processes, but also, in the future, to develop new ways of assisting infertile couples. Using embryonic stem cells, theoretically capable of transforming into any type of cells, several research groups have achieved some success in recent years, but no one has been able to get viable germ cells.

Recently, scientists from the University of Kyoto (Kyoto University) have found a way to reprogram the mouse embryonic stem cells into spermatozoon precursor cells and, using the resulting sperm, get normal mice. Their research can eventually lead to the development of fundamentally new methods of treating male infertility. However, as the team leader biologist Mitinori Saitou (Mitinori Saitou) believes, this will require solving several "very complex" technical and ethical issues.

As is known, spermatozoa and ovules develop from primary, or primordial, sex cells (primordial germ cells, PGCs). Primordial sex cells are formed in the early stages of embryogenesis from the mass of cells called epiblast. A few years ago, scientists learned to take epiblast cells from a mouse embryo and transform them into epiblast stem cells that can be regenerated in a laboratory for a long time. Researchers hoped that such cells can be used to produce primordial germ cells and, ultimately, spermatozoa and eggs. But, despite years of experiments, no one succeeded. Japanese scientists came to the conclusion that when the epiblast stem cells obtained in the laboratory acquire the ability for prolonged growth, they lose the ability to form sex cells.

Therefore, changing the approach, they decided to cultivate mouse embryonic stem cells in a cocktail of growth factors to get cells close to epiblast cells that live only a few days. The researchers found that 2-day cells can be used to produce cells that are close to primordial germ cells. Introduced in the testes of mice unable to produce their own sperm, such primordial stem cells ripened into spermatozoa, which successfully fertilized the ovules in vitro experiments. Scientists implanted the resulting embryos to surrogate mothers who produced normal offspring. Those born in this unusual way of mice grew up in fertile females and males and later also gave healthy offspring. In a similar way, prolific progeny can also be obtained from induced pluripotent stem cells (induced pluripotent stem cells, iPSCs) differentiated from adult skin cells.

"All I can say is" wow "! It's a breakthrough! ", Commented Orly Lacham-Kaplan, a specialist in reproductive biology from Monash University in Australia.

This work provides evidence that "primordial stem cells derived from embryonic stem cells can develop into functional germ cells," concurs Amander Clark, a biologist at the University of California in Los Angeles Angeles), who called the work of Japanese researchers "a decisive breakthrough in our understanding of the principles of development of sex cells."

According to Sait, scientists have to bypass many more obstacles. They would like to learn how to conduct the entire process of obtaining mature spermatozoa directly in the laboratory, rather than introducing similar primordial sex cells into the testes for maturation. Another goal is to get in vitro egg cells. Not only to understand the process itself, but ultimately to try to help infertile women. But, first of all, to transfer the results of their work to the clinic, it is necessary to establish whether the "recipe" that they found so successful for stem cells of mice will work on human cells.

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