Researchers at Washington State University have discovered a gene specific to male testes that could lead to the development of a highly effective, reversible, and non-hormonal male contraceptive for both humans and animals. The gene, known as Arrdc5, is expressed in the testicular tissue of mice, pigs, cattle, and humans. When the gene was knocked out in mice, male infertility resulted, impacting sperm count, movement, and shape.

The study, published in the journal Nature Communications, identified the Arrdc5 gene as being expressed only in testicular tissue, and in multiple mammalian species. When the gene was inactivated or inhibited in males, the sperm produced could not fertilize an egg, making it an ideal target for male contraceptive development. Importantly, lack of the gene also causes significant infertility, creating a condition called oligoasthenoteratospermia or OAT, which is the most common diagnosis for human male infertility. In the study, male mice lacking the 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.

Disrupting the protein encoded by the Arrdc5 gene would not require hormonal interference, which is a significant hurdle in male contraception. The protein could be targeted by a drug, making the contraceptive easily reversible. As the gene is found across mammalian species, the discovery also holds promise for use in animals, potentially replacing castration as a way to control reproduction in livestock or to limit overpopulation of wildlife species. The initial focus, however, is on giving humans more control over their own reproduction. With more than half of pregnancies worldwide still unintended, according to the United Nations, the development of an effective male contraceptive could have far-reaching impacts.

The research team will work on designing a drug that would inhibit the production or function of the protein encoded by the Arrdc5 gene. They have filed a provisional patent for the development of a male contraceptive based on this gene and the protein it encodes. The study received support from the National Institutes of Health and WSU's Functional Genomics Initiative.

Sources and References

• Washington State University
  New genetic target for male contraception identified 

• Nature Communications
  ARRDC5 expression is conserved in mammalian testes and required for normal sperm morphogenesis