Scientists are developing a male contraceptive drug which can inhibit the process of sperm development. When tested on rats, it blocked the links to the cells which nurture developing sperms, causing infertility to the animals. According to US and Italian researchers, they used relatively low doses of the molecule and found no obvious side effects, and the effect was even reversible. However, there is still much work to be done in order to determine if the approach will be equally effective and safe in men.
Researchers are now breaking down the different processes involved in fertilization starting from how men produce sperm. One area of study is focused on Spermatogenesis, the process of sperm development from spermatogonia to spermatozoa. During this process, the sperm cells sit next to other cells, called Sertoli cells, which nurse and help them grow. Breaking the connection between these two types of cells can result in infertility. Authors of the study used a recently developed molecule called Adjudin to dislodge the developing sperm from the Sertoli cells. Contraception happens when Adjudin disrupts the process of sperm maturation in the testes. It changes the way Sertoli cells interact with sperm. In normal sperm production, Sertoli cells divide to produce new sperm cells. They remain connected with immature sperm and nurse them through a series of microscopic bridges and channels. These bridges provide materials and information needed to direct the development of the immature sperm (spermatids).
In order to become functional sperm, these spermatids must undergo a series of cellular changes. However, when the rats were treated with Adjudin, the bridges between Sertoli cells and spermatids broke even before the processes of maturation were completed. The premature sperm were molecularly incomplete and were not capable of fertilizing an egg.
Since Adjudin is known to be toxic at high doses, researchers linked it chemically to a hormone, called FSH (follicle-stimulating hormone), which acts in the testicles where sperm are made. The FSH are made inactive so it would merely act as a carrier and not cause any effect itself, and delivered Adjudin to where it was needed, allowing much lower doses to be given.
As a result, the developing sperm cells "fall off" too early, even before they were properly mature, leading to complete but temporary infertility in the rats. Although the approach looks very promising, more research is needed to assess if the same could work in humans. Nonetheless, researchers and scientists alike welcome the concept and anticipate that the compound could become a male contraceptive treatment in the near future.
According to Dr. Richard Anderson of the University of Edinburgh, “ A non-hormonal approach to male contraception using a drug which specifically targets a process in spermatogenesis has long been a very attractive option, as it leaves hormone production by the test is intact.” He said it appeared that the drug effects could be fully reversible, although only a single dose was given in the study. He also added that Adjudin may be ineffective in men, as the biochemistry of the cell junctions it targets may be different, and the precise molecular basis of its mechanism of action is unknown. “However, perhaps the most important aspect of this study is the demonstration that using FSH targeting, drugs that are otherwise too toxic, can be delivered in safe yet effective doses.”
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