Male Contraceptive Pill - Stops Sperm from Developing

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SCIENCE NEWS
October 29, 2006
Potential Male Contraceptive Homes in on Testes

In a new approach to male contraception, a compound that interferes with sperm development causes infertility in rats.
Unmooring sperm from their source of nourishment in the testis might become the basis for a form of male contraception. Researchers have designed a compound that homes in on the testis and prevents sperm from accessing a key tissue, halting their development. In mice that were fed the compound, fertility dropped to zero after a few weeks without causing the animals noticeable harm.

The first generation of male contraceptives will likely employ hormones to block spermatic development. Such products are currently undergoing extensive clinical testing. But for men who don't want to alter their sex hormones over the long haul, researchers are exploring a variety of nonhormonal options based on sperm biology. One avenue involves protein-based adherens junctions, which allow sperm to attach to specialized cells in the testes. Similar to the brain, the testes do not allow blood to flow inside. To make up for the lack of circulatory nourishment, sperm cells adhere to so-called Sertoli cells, which provide the nutrients a growing sperm needs to reach maturity.


Biomedical researchers at the Population Council identified a compound that interferes with adherens junctions. Initially, some rodents that were fed the drug, dubbed Adjudin, experienced inflamed livers and muscle deterioration. In a Nature Medicine paper published online October 29 the researchers report they linked Adjudin to an engineered version of follicle stimulating hormone (FSH), a sex hormone recognized by receptors found only on the Sertoli cells. That way the Adjudin is dragged with FSH directly to the testes and spends less time circulating in the rest of the body, says senior team member Yan Cheng. As a result, much less of the compound is needed to reduce fertility in rodents, the group reports. The drug still needs several years of animal testing before a human trial is conceivable, Cheng says.

"It's certainly an imaginative and interesting approach, and potentially opens a new area in thinking about male contraception," says reproductive endocrinologist William Bremner of the University of Washington. Other nonhormonal approaches to male contraception target different aspects of the sperm's life cycle, such as by nullifying their ability to swim or attach to eggs, or by using a small plug to physically block their ejaculation. All these methods are in early stages of development and would require primate and human studies to prove their safety and efficacy, says Bremner. "That's potentially doable," he adds. --JR Minkel




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Sperm-busting male contraceptive pill in the pipeline
Men's Health News
Published: Monday, 30-Oct-2006
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Scientists are in the process of developing a male contraceptive drug which stops the development process of sperm.
The team from the U.S. and Italy have conducted tests on rats which block the connections to cells which "nurture" developing sperm.

The process makes the animals infertile and the researchers say that the low doses of the molecule used meant there were no obvious side effects, and the effect was reversible.

But biomedical researchers at the Population Council in New York say more research is needed to establish if the approach is equally effective and safe in men.

During spermatogenesis, when sperm are being made in the body, the sperm establish themselves next to other cells, called Sertoli cells, which nurse and help them flourish.

When the connection between these two cell types is broken, the result can be infertility in men.

For their study the scientists used a recently developed molecule called Adjudin to dislodge the developing sperm from the Sertoli cells.

Adjudin is known to be toxic at high doses and in order to avoid the toxic effects the researchers linked it chemically to a hormone, called follicle-stimulating hormone (FSH), which is critical for sperm production. It supports the function of Sertoli cells, which in turn support many aspects of sperm cell maturation.

The researchers rendered the FSH inactive so it would merely act as a carrier and not cause any effect itself, but delivered the Adjudin to where it was needed, which allowed much lower doses to be given.

This action made the developing sperm cells drop off before they were properly mature, resulting in complete but temporary loss of fertility in the rats.

The researchers, led by Dr. Dolores Mruk, from the Center For Biomedical Research in New York, anticipate that the compound could become a male contraceptive for human use.

Experts in the field say a non-hormonal approach to male contraception using a drug which specifically targets a process in spermatogenesis is very promising.

Senior team member of the research team at Population Council Yan Cheng says the drug still needs several years of animal testing before a human trial is conceivable.

Scientists have been unable to develop a male contraceptive pill because a man naturally produces about 150 million sperm cells each day of his adult life.

The results of the trial are published in the journal Nature Medicine.