Scientists at Washington State University have made a significant breakthrough in the search for non-hormonal male contraception. They have discovered a new gene, Arrdc5, expressed only in the testicular tissue of multiple mammalian species including mice, pigs, cattle, and humans.
This gene is specific to the male testes and when inactivated in male mice, it results in infertility by impacting the sperm count, mobility, and shape. The researchers have detailed their findings in the respected scientific journal Nature Communications.
This new discovery could lead to the development of a highly effective, reversible, and non-hormonal male contraceptive for use in humans and animals.
“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,” points out senior author Jon Oatley. “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.”
Although several molecular targets have been identified for male contraceptive development, the Arrdc5 gene is distinctive in that it is specific to the male testes and is found in multiple mammalian species.
Notably, the lack of the Arrdc5 gene can result in significant infertility, leading to a condition known as Oligoasthenoteratospermia (OAT). OAT is the most common diagnosis for human male infertility and is characterized by a decrease in the number of sperm produced, reduced mobility, and distorted shape, resulting in an inability to fertilize an egg.
In the recent WSU study, male mice that lacked the Arrdc5 gene produced 28% fewer sperm, which moved 2.8 times slower than normal mice, and almost all of their sperm had abnormal heads and mid-pieces. The study indicates that the protein encoded by the Arrdc5 gene is essential for normal sperm production. The research team, led by Professor Oatley, will now focus on developing a drug that can inhibit the production or function of this protein, which could pave the way for a highly effective male contraceptive.
Unlike other male contraceptive methods, disrupting the protein encoded by the Arrdc5 gene would not require hormonal interference. This is significant because testosterone, the hormone responsible for sperm production, also plays a crucial role in building bone mass, muscle strength, and red blood cell production in men. By targeting this protein with a drug, it would be possible to develop a highly effective male contraceptive that is easily reversible.
This is a crucial advantage since the ability to restore fertility quickly after discontinuing a contraceptive method is an essential factor for many men when considering their contraceptive options.
“You don’t want to wipe out the ability to ever make sperm – just stop the sperm that are being made from being made correctly,” he adds. “Then, in theory, you could remove the drug and the sperm would start being built normally again.”
Professor Oatley and Mariana Giassetti, the lead author of the study, have submitted a provisional patent for the development of a male contraceptive based on the Arrdc5 gene and the protein it encodes. This discovery holds promise not only for humans but also for animals, as the gene has been found in nearly every known mammal species.
This opens up possibilities for developing male contraception for use in livestock, potentially replacing castration as a means of controlling reproduction. In wildlife, it could be used to manage population overgrowth of certain species.
With this new knowledge, researchers could develop highly effective and safe male contraceptives that can be used in both humans and animals, leading to a significant breakthrough in reproductive health.
Although the discovery of the Arrdc5 gene has significant implications for animal reproductive management, the primary focus of the research is to provide greater control over human reproduction. Despite the availability of various forms of birth control for women, unintended pregnancies still account for over 50% of all pregnancies worldwide, as reported by the United Nations.
“Developing a way to curb population growth and stop unwanted pregnancies is really important for the future of the human race,” adds Oatley. “Right now, we don’t really have anything on the male side for contraception other than surgery and only a small percentage of men choose vasectomies. If we can develop this discovery into a solution for contraception, it could have far-ranging impacts.”
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