The discovery of a hormone-free way to immobilize sperm in mice could lead to the development of oral contraceptives for men. (This image actually shows Eucalyptus macrocarpa stamens under high magnification, which somewhat resemble sperm cells swimming en masse.) Image: flickr/Squil
The serendipitous finding that a potential cancer-fighting compound temporarily halts sperm production in mice has seeded new hopes for a reversible male contraceptive pill. At a time when the only non-hormonal contraceptive choices for men consist of condoms and vasectomies, the finding, published today in the journal Cell, has stirred the interest of pharmaceutical companies, although it’s quite far from entering clinical trials.
Several new contraceptives that rely on steroid hormones are in the works to reduce sperm production in men. However, most products developed to date seem to carry undesirable side effects, such as acne and perturbations of cholesterol levels. So, scientists have sought to halt sperm production with compounds that do not alter hormones, targeting everything from calcium ion channels on the tails of sperm to the production of retinoic acid, a metabolite of Vitamin A that has a role in their development. A team led by Dolores Mruk at the Population Council’s Center for Biomedical Research in New York has even reported in Nature Medicine on the discovery of a chemical compound known as Adjudin that can stop sperm-forming cells from adhering to the Sertoli cells that nurture them.
The new findings announced today also describe a non-hormonal drug for stopping sperm—but contraception was the furthest thing from the minds of James Bradner and his colleagues at the Dana-Farber Cancer Institute who initially developed the experimental compound.
As we reported last year, Bradner’s team had investigated a small molecule called JQ1 for its ability to thwart cancer by acting on a protein named BRD4. They showed success in mice with multiple myeloma, and other groups soon reported similar findings in animal models of leukemia and lymphoma. Bradner has been downright evangelical about the drug ever since, shipping it to more than 250 labs worldwide, according to a profile of Bradner published last week in Nature.
As part of their homework in understanding the specificity of JQ1, Bradner’s group found that it also targeted a similar protein, called BRDT, which comes from a completely different chromosome than BRD4. In a quick survey of the scientific literature, Bradner noticed a study that linked mutations in BRDT to fertility problems in men, so he reached out to reproductive biologist Marty Matzuk of the Baylor College of Medicine in Houston to study its contraceptive effects in mice.