Pill for men: why a gene could be the breakthrough

It has been announced time and again for years, but never catches on: the pill for men. The reasons for this are diverse; Experts cite, among other things, conventional role models, the still male-dominated medicine, which has more understanding for men than for women, or the fact that men do not have to bear the biological consequences of reproduction. Be that as it may, contraception for men is not making progress.

But it is very well researched. However, research into hormonal preparations – analogous to the pill for women – suffered a major setback in 2011 when a large-scale study by the World Health Organization, in which sperm production was controlled by hormones, was stopped. Too many participants had complained of depression and mood swings.

Another angle can therefore promise more success: genetics. Intensive research is also being done in this area, but no decisive breakthrough has yet been achieved. Still, progress is being made, according to a new study from Washington State University, published in the scientific journal Nature Communications.

The research team led by Jon Oatley, professor of molecular biosciences, has discovered a gene that could serve as the key to male contraception. When it is inactivated, sperm count decreases and the shape and motility of the remaining sperm cells change so that they are no longer able to fertilize an egg.

The gene in question, which Oatley says is the most promising target in male contraception for years, is called ARRdc5. It is expressed in the testes of mice, pigs, cattle and humans. Tests on mice have now shown that they produce 28 percent fewer sperm cells when the gene is switched off. In addition, these spermatozoa moved 2.8 times slower than mice with a normally functioning Arrdc5 gene.

In addition, up to 98 percent of the sperm from mice without a functioning Arrdc5 gene showed an abnormal shape. Because of all these changes, the males without the Arrdc5 gene could no longer fertilize a female. “When this gene is inactivated or inhibited in men, they produce sperm that cannot fertilize an egg, and that is an important goal for male contraceptive development,” notes Oatley.

Arrdc5 – which is uniquely expressed in the male gonads, the testes, encodes a specific protein required for normal sperm production. By inactivating the gene, this protein is no longer produced and the gonads therefore produce less and abnormal sperm.

Oatley and his team see their success as a prelude to further research. Their goal is to find or possibly develop a drug that can prevent the production of the protein encoding Arrdc5 or disable its function.

What makes the identification of Arrdc5 and its function so promising is that there are no side effects associated with hormone treatment by inactivating the gene or stopping the production of the protein it encodes. With hormonal contraception, the side effects are a major stumbling block, because the male sex hormone testosterone also fulfills other functions in men in addition to sperm production, including building bone mass and muscle strength and producing red blood cells. blood cells.

Also, a birth control pill targeting the protein would not have an irreversible effect – men taking such a supplement would not be permanently infertile. “You don’t want to take away their ability to produce sperm,” Oatley points out. “You just want to prevent sperm being produced properly. Because then you can theoretically stop taking the pill, and then the sperm will be produced in the normal way again.”

Moreover, since Arrdc5 is not only found in the testes of humans, but also in the male gonads of almost all mammalian species, it could be an interesting target in the search for animal contraceptives. Such means could make the currently widespread but invasive castration of animals obsolete. Moreover, if a method were found to administer such contraceptives to wild animals, their population would be better controlled than by hunting. Infestation by pests can also be carefully prevented in this way.

At the moment, however, this is still a dream for the future. For now, researchers are focusing on developing a pill suitable for human use. “Developing a way to slow population growth and prevent unwanted pregnancies is very important for the future of humanity,” says Oatley. “Currently, apart from sterilization, there aren’t many options for men, and only a small percentage of men opt for this procedure. If we could develop this discovery into a contraceptive, it could have far-reaching consequences.” (i.e.)