Scientists identify potential new 'genetic target' to develop male contraception

Inactivating a gene is key to this development

The team identified an expression of the gene Arrdc5 to develop this genetic target-based contraception. This gene has been found in the testicular tissue of many different species, including mice, pigs, cattle, and humans. 

The Arrdc5 gene was inactivated in mouse models to study sperm performance. As a result, they discovered signs of infertility in male mice models. When the gene was removed, their sperm count dropped by 28 percent, and their sperm movement was found to be nearly 2.8 times slower than in normal mice. Surprisingly, the shape of the sperm changed, too, and depicted "abnormal heads and mid-pieces." 

“The study identifies this gene for the first time as being expressed only in testicular tissue, nowhere else in the body, and it’s expressed by multiple mammalian species. When this gene is inactivated or inhibited in males, they make sperm that cannot fertilize an egg, and that’s a prime target for male contraceptive development,” explained Oatley. 

This is the first time that such a method has been identified that reduces sperm count while also ensuring that the individual does not lose the ability to produce sperm in the future. The team has theorized: “You could remove the drug and the sperm would start being built normally again,” added Oatley.

In addition, as this gene is found in many mammalian species, researchers hope that this method can be applied to animals. This new method may pave the way for the development of male contraception for use in livestock to limit species overpopulation in the future.

Following this study, the team's focus will be on developing a drug that will inhibit the functioning of a protein encoded by this gene. In the future, this male contraceptive has the potential to reduce population growth and prevent unwanted pregnancies across the world.

Study abstract:

In sexual reproduction, sperm contribute half the genomic material required for creation of offspring yet core molecular mechanisms essential for their formation are undefined. Here, the α-arrestin molecule arrestin-domain containing 5 (ARRDC5) is identified as an essential regulator of mammalian spermatogenesis. Multispecies testicular tissue transcriptome profiling indicates that expression of Arrdc5 is testis enriched, if not specific, in mice, pigs, cattle, and humans. Knockout of Arrdc5 in mice leads to male specific sterility due to production of low numbers of sperm that are immotile and malformed. Spermiogenesis, the final phase of spermatogenesis when round spermatids transform to spermatozoa, is defective in testes of Arrdc5 deficient mice. Also, epididymal sperm in Arrdc5 knockouts are unable to capacitate and fertilize oocytes. These findings establish ARRDC5 as an essential regulator of mammalian spermatogenesis. Considering the role of arrestin molecules as modulators of cellular signaling and ubiquitination, ARRDC5 is a potential male contraceptive target.