Researchers investigated the role of the Arrdc5 gene in mice with the gene inactivated via CRISPR/Cas9 genome editing. These mice were found to have 72 percent lower sperm counts, and 98 percent of the sperm they did produce had malformations in the head of the sperm and were less able to fertilise female egg cells during IVF and ICSI. Tissue expression analysis revealed that Arrdc5 RNA is exclusively detectable in the testes of mice, cattle and pigs and is highly enriched in human testes.
Senior author of the study Professor Jon Oatley from Washington State University, said: 'The study identifies this gene for the first time as being expressed only in testicular tissue, nowhere else in the body. When this gene is inactivated or inhibited in males they make sperm that cannot fertilise an egg, and that's a prime target for male contraceptive development.'
Although the function of Arrdc5 in sperm production remains unclear, inactivation of this gene in male mice was found to disrupt a sperm cell maturation process known as capacitation. Capacitation results in the sperm cell being able to fuse with the egg cell membrane and fertilise it, as well as inducing activation of the sperm tail to enable intrauterine navigation.
Publishing their results in Nature Communications, the researchers investigated the ability of sperm from male mice with this gene inactivated to fertilise egg cells using IVF and ICSI. They found that IVF using these sperm resulted in 5.5 times fewer blastocysts, and ICSI resulted in 7.5 times fewer blastocysts than those created with sperm from wild type mice.
If a drug could be identified or developed which targets the proteins created by this gene, this could lead to the development of a new, male-controlled form of contraception, researchers suggested. They have filed for a patent to further investigate Arddc5 within this context.
Professor Richard Anderson, of the University of Edinburgh, who was not part of the study, said: 'The last couple of years has seen a very encouraging uptick in really promising new targets for a "male pill". This study identifies a novel gene which clearly has a major role in sperm production.
'Sperm production was low, those sperm that were produced didn't function, and the male mice were completely infertile, but otherwise healthy. So [it's] very interesting.'