Discovery of a gene in multiple mammalian species could pave the best way for a highly effective, reversible and non-hormonal male contraceptive for humans and animals.

Washington State University researchers identified expression of the gene, Arrdc5, within the testicular tissue of mice, pigs, cattle and humans. Once they knocked out the gene in mice, it created infertility only within the males, impacting their sperm count, movement and shape. The researchers detailed their findings within the journal Nature Communications.

The study identifies this gene for the primary time as being expressed only in testicular tissue, nowhere else within the body, and it’s expressed by multiple mammalian species. When this gene is inactivated or inhibited in males, they make sperm that can’t fertilize an egg, and that is a major goal for male contraceptive development.”

Jon Oatley, senior creator and professor in WSU’s School of Molecular Biosciences

While other molecular targets have been identified for potential male contraceptive development, the Arrdc5 gene is restricted to the male testes and located in multiple species. Importantly, lack of the gene also causes significant infertility making a condition called oligoasthenoteratospermia or OAT. This condition, probably the most common diagnosis for human male infertility, shows a decrease in the quantity of sperm produced, slowed mobility and distorted shape in order that the sperm are unable to fuse with an egg.

Within the WSU study, the male mice lacking this gene produced 28% less sperm that moved 2.8 times slower than in normal mice – and about 98% of their sperm had abnormal heads and mid-pieces.

The study indicates that the protein encoded by this gene is required for normal sperm production. Oatley’s team will next work on designing a drug that will inhibit production or function of that protein.

Disrupting this protein would not require any hormonal interference, a key hurdle in male contraception since testosterone plays other roles beyond sperm production in men including constructing bone mass and muscle strength in addition to red blood cell production. Designing a drug to focus on this protein would also make it easily reversable as a contraceptive.

“You don’t need to wipe out the flexibility to ever make sperm – just stop the sperm which can be being constructed from being made accurately,” he said. “Then, in theory, you may remove the drug and the sperm would start being built normally again.”

Oatley and study first creator Mariana Giassetti have filed a provisional patent for the event of a male contraceptive based on this gene and the protein it encodes.

Since the gene is found across mammalian species, this information also holds promise to be used in animals, Oatley said. The team analyzed available biological data on DNA and protein sequences in mammals and located the gene in almost every known mammal species. This opens the potential to develop male contraception to be used in livestock, perhaps replacing castration in some instances as a option to control reproduction, and in wildlife when managers seek to limit overpopulation of a species.

The initial focus, nevertheless, is on giving humans more control over their very own reproduction. While there are lots of types of contraception for ladies, they usually are not at all times effective or widely available, and greater than half of pregnancies worldwide are still unintended, based on the United Nations.

“Developing a option to curb population growth and stop unwanted pregnancies is actually vital for the longer term of the human race,” said Oatley. “At once, we do not really have anything on the male side for contraception aside from surgery and only a small percentage of men select vasectomies. If we are able to develop this discovery into an answer for contraception, it could have far-ranging impacts.”

This study received support from the National Institutes of Health and WSU’s Functional Genomics Initiative, a multi-year university investment to support development of genetic technology research.