Scientists discover new genetic target for male contraception

The discovery of a gene in several species of mammals could pave the way for a male contraceptive highly effective, reversible and non-hormonal. This is what reveals a new study conducted by researchers at Washington State University (WSU), in the United States.

The scientists identified the expression of a gene, called Arrdc5, in the testicular tissue of mice, pigs, cattle and humans. Knocking out the gene in mice in one trial led to infertility in males only, affecting sperm count, motility and shape. The results were published in the scientific journal Nature Communications.

“The study identifies this gene for the first time as being expressed only in testicular tissue, nowhere else in the body, and it is expressed by several mammalian species,” said Jon Oatley, senior author and professor in WSU’s School of Molecular Biosciences, in a statement. “When this gene is inactivated or inhibited in males, they produce sperm that cannot fertilize an egg, and this is the main target for the development of male contraceptives.”

Although other molecular targets have been identified for the potential development of male contraceptives, the Arrdc5 gene is specific for male testes and found in several species.

Experts point out that missing the gene also causes significant infertility, creating a condition called oligoasthenoteratospermia. This condition, the most common diagnosis for human male infertility, shows a decrease in the amount of sperm produced, reduced motility and distorted shape, such that the sperm are unable to fuse with an egg.

In the WSU study, male mice lacking this gene produced 28% fewer sperm that moved 2.8 times slower than normal mice — and about 98% of their sperm had abnormal heads and midpieces.

The study indicates that the protein encoded by this gene is necessary for normal sperm production. The next steps include developing a drug that inhibits the production or function of this protein.

Disrupting this protein would not require any hormonal interference, a key hurdle in male contraception, as testosterone plays roles other than sperm production in men, including building bone mass and muscle strength, as well as producing red blood cells. Designing a drug to target this protein would also make it easily reversible as a contraceptive.

“You don’t want to end up with the ability to produce sperm – just prevent the sperm that is being produced from being produced properly,” he said. “So, in theory, you could remove the drug and sperm would start to form normally again,” details Oatley.

Researcher Jon Oatley and the first author of the study, Mariana Giassetti, registered a provisional patent for the development of a male contraceptive based on this gene and the protein it encodes.

As the gene is found in mammalian species, this knowledge also holds promise for use in animals, says Oatley.

The team analyzed available biological data on DNA and protein sequences in mammals and found the gene in nearly every known mammalian species. This opens up the potential to develop male contraception for use in livestock, perhaps replacing castration in some cases as a way to control reproduction, and in the wild when there is a need to limit overpopulation of a species.

However, scientists say the initial focus is on giving humans more control over their own reproduction. While there are many forms of birth control for women, they are not always effective or widely available, and more than half of pregnancies worldwide are still unintended, according to the United Nations (UN).

“Developing a way to contain population growth and stop unwanted pregnancies from arising is really important to the future of the human race,” said Oatley. “Right now, we don’t really have anything on the male side of contraception other than surgery and only a small percentage of men choose vasectomy. If we can develop this discovery into a solution for contraception, it could have far-reaching impacts.”