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Tuesday, December 17, 2013

Toward a male contraceptive

A safe, reversible, effective male contraceptive is almost the white whale of reproductive health. Thanks to work by Carl White from Monash University and his colleagues, there may soon be one. At least if you’re a mouse.
Over the years, there have been many efforts to create a male contraceptive. Most of these have used hormonal methods that focus on eliminating and/or debilitating sperm so that there can be no fertilization. Unfortunately, such strategies tend to have one or more serious drawbacks. They can be irreversible, they can increase the risk for birth defects in any future children, and they often have undesirable side effects on male sexuality.

White and his colleagues came at it from a different angle. They decided to block the movement of sperm through the vas deferens. This is a tube leading from the testis, where sperm is produced, to the urethra in the penis. When men have vasectomies, it is their vasa deferentia that are permanently severed. While vasectomies are usually highly effective, they're difficult or impossible to reverse.

Diagram of the ducts of the male reproductive system

The movement of sperm through the vas deferens isn’t a passive process, rather, the sperm are actively propelled by contractions within the vas deferens. Those contractions are caused by the activation of special receptor proteins embedded along the length of the vas deferens. In male mice bred without such receptors, there is no contraction of the vas deferens and the movement of sperm is stalled. This lack of sperm movement was 100% effective in preventing pregnancy.

To be clear, there’s nothing wrong with the sperm. They just can’t get to the business end of the penis. Sperm that was removed from these receptor-less mice were perfectly normal and capable of fertilizing mouse egg cells and making healthy baby mice. The adult male mice that were missing the receptors also seemed to be fine. Behaviorally, the altered mice were no different than the control mice. Their health was not compromised and nor was their appreciation for the lady mice.

While the mice used in this study were born with dysfunctional vas deferens receptors, there are also drugs that can block those receptors and they can be administered orally. I’m sure this will be much preferred over the currently being tested RISUG male contraceptive, since that one has to be injected directly into the penis.

Although White’s method sounds extremely promising, there is one potential problem. The same receptors that are in the vas deferens are also present in many other structures, including blood vessels and nerve cells. The mice didn’t appear to be harmed by the disabling of those receptors, but extreme caution should be used before starting any human trials.

White CW, Choong YT, Short JL, Exintaris B, Malone DT, Allen AM, Evans RJ, & Ventura S (2013). Male contraception via simultaneous knockout of α1A-adrenoceptors and P2X1-purinoceptors in mice. Proceedings of the National Academy of Sciences of the United States of America PMID: 24297884.

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