Spermatogenesis as solution of infertility
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Spermatogenesis as solution of infertility

Many researchers are trying to replicate the process of spermatogenesis (sperm production process). Conclusive experiments on mice hold promise for humans.

All over the world, researchers are trying to reproduce in test tubes the cycle of spermatogenesis. Different approaches are tested for fifteen years. If science seeks to copy this complex process, it is in order to offer solutions to people suffering from certain forms of infertility and assisted reproduction that can do nothing.

Approximately 1% of men suffering from azoospermia, that is to say, they do not produce sperm. Two causes may be responsible. Or they do not have in their germ cells of the testes (the cells may be transformed into spermatozoa). Either they lack the “machinery” that allows these biological germ cells to evolve and become sperm. An accident, chemotherapy or the fact that the testicles are not “down” before birth (cryptorchidism) may explain this abnormality. In 40% of cases, however, the causes of azoospermia remain undetermined.

74 days of maturation

But let everything from the beginning. At the origin of each individual, there is a meeting between an egg (released from the ovary in women) and sperm after sex. Sperm production, meanwhile, is following a complex and lengthy process of 74 days: the spermatogenesis. It takes place at puberty and continues throughout adulthood.

To become sperm able to fertilize the egg, the male germ cells will have to go through different stages highly regulated within the seminiferous tubules in the testes. This is big “factories” that allow the production of sperm: the germ cells grow there, take a form of “tadpole” acquire their flagellum (their “tail”), then start to move. They also dispose of a half of each of their chromosomes to grow into spermatozoa. The process is so delicate that many mistakes can stop it and cause infertility.

Yet despite the complexity of this process, a start-up Lyon announced last September have passed, the world’s first laboratory to obtain complete human sperm from germ stem cells. How? By creating a unique culture device in three dimensions, which is built as a copy of the seminiferous tubules where applicable spermatogenesis. In this device, the researchers reproduced an environment rich in nutrients and hormones necessary for the production of reproductive cells.

If it looks promising, this research has yet been no serious publication. This proves that it did not convince the scientific community: “The scientific protocol is not clear, so that the project lacks credibility,” says Serge Nef, professor at the Faculty of Biology and Medicine the University of Geneva. An opinion shared by Laurent Vaucher, doctor responsible for consultation in andrology at the Lausanne University Hospital (CHUV). This confirms that so far “no one has published articles confirming that he was able to produce human sperm in vitro.”

Between research and safety

Nevertheless, looking ahead, and the field is expanding. Today, scientists are already able to create artificial sperm cells in animals. From immature testicular tissue samples from the mice, Japanese and American researchers managed to reproduce in vitro differentiation processes of male cells that occur during puberty. In vitro fertilization has generated, in a second time, fertile and healthy baby mice.

This technique offers clinical opportunities especially for children with cancer who are undergoing chemotherapy or radiotherapy. “These treatments can destroy germ cells and compromise their future fertility.

A testicular tissue prior freezing may allow to avoid using spermatogenesis in vitro fertilization techniques associated with in vitro, “explains Dr. Fabien Murisier, director of Fertas, romand specialized laboratory in the diagnosis of male infertility. But research in rodents is only one step in understanding these mechanisms. Not only spermatogenesis is simpler, but the ethical questions are less challenging than those faced with the manipulation of human material.

Other approaches seek to make any artificial process. By reproducing all stages of spermatogenesis, indeed, we understand the mechanisms that allow undifferentiated stem cells become reproductive cells. Researchers are also working on methods for obtaining reproductive cells from adult tissues such as bone marrow. “This type of research could eventually help patients completely deprived of germ cells to boost your fertility,” says Fabien Murisier yet.

Before practical applications are emerging – not until ten or twenty years at least, according to the approaches – many questions remain open. In particular as regards the safety of these techniques. The example of “Dolly” the cloned sheep born in 1996 who suffered from premature aging, showed that in vitro manipulations could affect the genetic and epigenetic individuals designed in this way and affect their health and fertility. The fact remains that this research carry much hope for parenting research in couples.

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