Historically, contraceptive options are greater for women than for men. While they rely on birth control ranging from oral pills to patches and intrauterine devices, the main options for them are condoms and vasectomy.
As a result, the responsibility of preventing pregnancy also hangs unequally on women, in addition to the discomfort and side effects of available female contraceptives.
Researchers at the University of Minnesota, in the United States, presented results of the study of a non-hormonal male contraceptive that was able to prevent pregnancy in mice, without presenting side effects. The findings were presented at a meeting of the American Chemical Society (ACS).
Currently, men have two effective birth control options: male condoms and vasectomy, the surgical procedure being considered a permanent form of male sterilization. While vasectomies can sometimes be reversed, reversal surgery is expensive and not always successful.
The need for an effective and long-lasting contraceptive, similar to the contraceptive pill for women, has mobilized the scientific community. “Scientists have been trying for decades to develop an effective male oral contraceptive, but there are still no approved pills on the market,” said researcher Abdullah Al Noman, who was part of the study.
Among the compounds currently evaluated in clinical trials are those that target the male sex hormone testosterone. However, hormonal changes can lead to side effects such as weight gain, depression, and increased levels of low-density lipoprotein cholesterol (known as LDL).
“We wanted to develop a non-hormonal male contraceptive to avoid these side effects,” says Noman, a graduate student.
How the contraceptive was developed
To develop the non-hormonal male contraceptive, the researchers targeted a protein called retinoic acid receptor alpha (RAR-α). This protein is part of a family of three nuclear receptors that bind to retinoic acid, a form of vitamin A that plays important roles in cell growth, differentiation (including sperm formation) and embryonic development.
THE deletion of the RAR-α gene in male mice makes them sterile, with no immediate side effects. Although other scientists have developed oral compounds that inhibit all three members of the RAR family (RAR-α, -β, and -γ), causing reversible sterility in male mice, the Minnesota team sought to find a drug that was specific for RAR-α. and therefore less likely to cause side effects.
Thus, the scientists closely examined the structures of RAR-α, -β and -γ bound to retinoic acid, identifying structural differences in the binding ways the three receptors bind. With this information, they designed and synthesized approximately 100 compounds and evaluated their ability to selectively inhibit RAR-α in cells.
They identified a compound, which they named YCT529, which inhibited RAR-α almost 500 times more potently than RAR-β and -γ. When given orally to male mice for four weeks, the YCT529 dramatically reduced sperm count and was 99% effective in preventing pregnancy, with no observable side effects. Mice could generate pups again 4 to 6 weeks after receiving the compost.
According to researcher Gunda Georg, coordinator of the study, YCT529 will start being tested in human clinical trials in the third or fourth quarter of 2022. “As it can be difficult to predict whether a compound that looks good in animal studies will also work right in human trials, we are currently exploring other compounds as well,” she said in a statement.
Brazilian research
Researchers from the Universidade Estadual Paulista (Unesp) discovered, from the study of a protein existing in the sperm, two new targets that, combined, can be used for the development of contraceptives for men.
The focus of the research is EPPIN, an acronym for epididymal protease inhibitor, whose main function is to modulate the ability of sperm to swim to the egg, called motility. Scientists are looking to develop contraceptives that act on sperm motility, since it is more difficult to come up with a drug capable of preventing the production of the male gamete.
In the research conducted at Unesp, mice received three types of antibodies to verify if they bound to EPPIN and blocked sperm motility. By binding to the target molecule, the antibodies showed in which domains of the protein there should be an intervention to reduce or prevent sperm motility.
The research results were published in the scientific journal Molecular Human Reproduction.
(With information from the American Chemical Society and Agência Fapesp)
Source: CNN Brasil
