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Male Contraceptive Can Stop Sperm in Their Tracks


By Anette Breindl
Science Editor

Researchers have identified a strategy for a male contraceptive that interferes with sperm transport rather than production – an approach that may allow for a reversible male method of contraception. Researchers have been trying to develop oral contraceptives for men for some time – but attempts so far have failed, though for different reasons.

“Historic attempts at male contraception have either been hormonal to disrupt sperm production or aimed at disrupting sperm production to produce dysfunctional sperm,” Monash University’s Sabatino Ventura told BioWorld Today.

But both those strategies have major drawbacks. “Hormonal strategies are problematic because they affect sexual behavior and function as well as masculinity thus producing intolerable side effects. “

More recently, attempts have focused on interfering with sperm development. But those approaches, too, have drawbacks.

“Developmental approaches have problems as they are difficult to reverse and may lead to genetic defects in future offspring,” Ventura said.

And is some cases, they may also face psychological barriers. One recent strategy of blocking sperm production lead to animals with noticeably smaller testicles. At the time those studies were published, senior author James Bradner told BioWorld Todaythat the slide showing those smaller mouse testicles “always induces some level of discomfort among half the audience.” (See BioWorld Today, Aug. 17, 2012.)

And so, male contraceptive options remain limited to condoms and vasectomies. The latter are quite frequent – the procedure is performed hundreds of thousands of times annually in the U.S. alone – suggesting that there is a market for male contraceptives.

In their experiments, which were published in the Dec. 2, 2013, online, issue of the Proceedings of the National Academy of Sciences, Ventura and his team decided to look at the viability of an alternative approach, namely, preventing sperm from getting out of the male reproductive tract and into the female one during ejaculation.

Ventura and his team disrupted that transport by knocking out two autonomic nervous system receptors, alpha 1A-adrenergic receptor and P2X1-purinoceptor. Blocking those receptors separately reduces fertility, but not to a degree that would be useful as a contraceptive. So the scientists tested the effects of blocking both simultaneously.

“The two receptors that we knocked out mediate smooth muscle contraction,” Ventura explained, and during sex, “they are important in mediating contractions of the vas deferens to transport sperm.” Double knockout male mice produced normal sperm that was able to fertilize eggs in vitro, and when those eggs were implanted into surrogate mothers they ultimately resulted in apparently normal litters.

The mice also showed normal levels of sexual activity. In fact, in their paper, the authors noted that given their vasodilatory effects, inhibitors of the two receptors “are likely to improve erectile function and premature ejaculation.”

The alpha-1 adrenergic blocker Dibenzyline, which is used to treat hypertension, has been tested as an oral contraceptive before, and Ventura and his team wrote in their paper that in that trial, “notably, all participants in this small trial wished to continue the medication.”

Whether the knockout mice were having better sex was beyond the scope of the experiments. But at any rate, dozens of matings did not lead to any baby mice.

The double knockouts had only minimally altered blood pressure and resting heart rate, suggesting that compensatory mechanisms kicked in in the knockouts.

“Inhibition of sperm transport by autonomic mechanisms is sufficient to produce male contraception,” Ventura concluded. “This is the first nonhormonal nongermline strategy, which has been successful in producing complete contraception.

“The fact that the health of sperm is not compromised,” he added, “also indicates that this strategy could be easily reversed if achieved by chemical means,” although confirming this will take inducible knockouts or pharmacological blockers of the purinoreceptor target – “there are already drugs to block the adrenoceptor target.”

Once an inhibitor of the purinoreceptor is identified, “we need to show that we can achieve the same level of contraception by chemical (pharmacological) means as we observed in our genetically modified mouse model.”