INCONCEIVABLE: In a new approach to male contraception, a compound that interferes with sperm development causes infertility in rats.
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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.