Stop that sperm!

There aren't a heap of options out there for guys wanting to take on the responsibility of non-baby making. But research is ongoing, and there are some promising leads for hormonal contraceptives, which work by interfering with the production of sperm. There are also non-hormonal methods, including the two options currently available to men: condoms and vasectomies. But are there others in the works?

Interfering with sperm production and development

Dietary Vitamin A (retinol) is needed for normal sperm production. Targeting the production in the testis of retinoic acid, which is made in the body from Vitamin A, would be an option for stopping sperm production.

Researchers at Colombia University carried out experiments giving mice drugs which targeted a receptor called ‘retinoic acid receptor α’. Not only did this cause infertility but, importantly, the mice stayed healthy and the effect was reversible. The long-term effects on people, however, aren’t yet known. And, because Vitamin A is needed throughout the body for cells to divide properly, contraceptives that target it would have to do so very precisely to avoid serious side effects.

Another approach is to use drugs to target Sertoli cells in the testes. A Sertoli cell is a tall, column-shaped cell found in the wall of the seminiferous tubule—the place where male sex cells are created. Sertoli cells are what’s known as ‘nurse’ cells—they supply the nutrients, hormones and chemicals needed by developing sperm. Men who don’t have Sertoli cells are infertile. The benefit of drugs that target Sertoli cells is that they may be able to be taken orally.

One example, being developed by the Population Council, is a chemical called Adjudin. It stops young sperm cells from sticking to Sertoli cells—and without Sertoli cells, the sperm can’t develop. However, when taken by mouth, a large dose is needed for it to work effectively, leading to side effects in the muscles and liver. Scientists are looking into better formulations but the research is still in its early stages.

Other research looks at proteins produced in the epididymis, the tube that joins the testicle to the vas deferens. Scientists are working on identifying and targeting proteins made in this area which sperm need to develop.

Australian scientists have examined proteins activated in the epididymis that help sperm bind to the egg. Some men have sperm that swim like champions, but they may still be infertile if they lack a special ‘chaperone’ protein (called HSP2A), which helps sperm recognise and stick to the egg. Better understanding the role of this protein would help us better understand male fertility and potentially provide a new contraceptive option.

Another approach involves mimicking proteins that slow sperm down. Eppin is a protein covering the sperm’s surface. Normally, another protein called semenogelin, found in seminal fluid, binds to Eppin and stops the sperm from swimming. The sperm only get going again when an enzyme called PSA removes the semenogelin protein, allowing it to swim towards the egg. Researchers have been working on a drug which mimics the effect of the semenogelin protein and, importantly, isn’t removed by the PSA enzyme.

Stopping sperm in its tracks

A kind of sperm ‘roadblock’ is one option being looked at for a number of potential new contraceptives for men. A physical barrier (such as a polymer gel) is injected into the vas deferens (the duct which carries sperm from the testis to the urethra) so the sperm is blocked from continuing on its journey to the ejaculatory ducts.

By blocking the vas, these methods work the same way as a vasectomy. The difference is that in a vasectomy the vas are cut and sealed—making it a pretty permanent solution difficult to reverse—but the blocking devices may be removed by a second injection that flushes out the gel. That means that fertility could potentially be restored—however, this is yet to be conclusively proven. RISUG (Reversible Inhibition of Sperm Under Guidance) is one such approach, developed in India. The non-profit Parsemus Foundation in the United States has developed a polymer hydrogel called Vasalgel, for which human trials are scheduled to begin in 2018 or 2019.

Preventing fertilisation

What if rather than stopping sperm production, or blocking its pathway, we let them go merrily on their way, and just step in right at the end of their journey to stop them actually entering the egg?

Usually, as the sperm reaches the egg, its swimming pattern changes: it starts lashing its tail about wildly, like a (slightly deranged) freestyler going for gold. This frantic movement is called ‘hyperactivation’ and is necessary for the sperm to reach and burrow into the egg. It’s triggered by the release of progesterone by the egg. A rush of calcium goes into the sperm’s tail, enabled by the opening of a calcium channel (a kind of ‘gate’ which lets electrically charged ions enter the sperm) known as CatSper. Scientists are looking into potential drugs which could block the action of CatSper. This would prevent hyperactivation—and the sperm would be unable to actually fertilise the egg. Sorry guys, but well done on making it this far.