Gene protein key to technique for ‘switching off’ male fertility

More than 60 years after the contraceptive pill arrived, scientists are finally making progress towards a male equivalent.

The female contraceptive pill has been available for more than 60 years.

More than 60 years after the contraceptive pill arrived, scientists are finally making progress towards a male equivalent.

The latest advance in the ­decades-long hunt for a safe, reliable and reversible contraceptive drug for men involves a gene called Arrdc5.

In experiments involving mice, scientists were able to use it like a switch: when the gene was disabled, males became infertile, though otherwise they appeared healthy.

It emerged that the gene produces a crucial protein, which plays a part in the final stages of sperm formation. Without it, sperm lose the ability to propel themselves forward and hence the ability to reach an egg to fertilise it.

The same gene is active in the testicles of humans, and Jon Oatley, of Washington State University, the senior author of the study, is now searching for a drug molecule that interferes with the protein. His team believes it should be possible to suppress or block it for a limited time, providing a reversible contraception.

David Elliott, of Newcastle University, who was not involved in the study, said the findings were intriguing and Arrdc5 protein appeared to be a good target.

“Hopefully the data will extrapolate to humans,” Professor Elliott said.

“Going forward, it will be important to find out more about the Arrdc5 protein and what it does that is so important for sperm function, and to develop ways this can be inhibited while causing minimal side effects.

“It is important to develop an effective male contraceptive to help men take more responsibility in birth control – including shouldering any potential side effects, which hopefully in most people are not serious.”

Male mice lacking the Arrdc5 gene produced 28 per cent les sperm, and the sperm that were created moved at only about a third of the speed of those in normal mice. About 98 per cent of the sperm had abnormal shapes.

Richard Anderson, of the University of Edinburgh, also not part of the study, said: “The last couple of years has seen a very encouraging uptick in really promising new targets for a ‘male pill’.”

“This study identifies a novel gene which clearly has a major role in sperm production,” Professor Anderson said. “Sperm production was low, those sperm that were produced didn’t function, and the male mice were completely infertile, but otherwise healthy. So [it’s] very interesting.”

He also said there were reasons to be cautious. Findings in mice are not guaranteed to be replicated in humans, he said. There was a “long way to go to make it a male contraceptive, but it could equally be a potential cause of infertility in some men,” he added.

The study, published in Nature Communications, is part of a push for male contraception.

Another team is focusing on a molecule that targets a specific enzyme, without which sperm cannot swim or mature.

When it was tested on mice, all attempts at impregnation failed, with the effects fully wearing off after 24 hours.

“Our dream is a pill the man takes half an hour before and it would keep him essentially infertile … for the next 16 hours,” ­Jochen Buck, from Weill Cornell Medicine, said this year.

Another male contraceptive in the works, Nestorone, requires the daily application of gel across the shoulders.

It uses hormones to halt sperm production for as long is it is used, but not once it is stopped.

Human trials have begun.

The Times