Key to male contraceptive

05 December 2013
Posted by Chris Smith.

A means to block male fertility that doesn't involve potentially harmful hormone treatments has been unveiled by researchers in Australia and the Sperm and EggUK.

A male equivalent of the female oral contraceptive pill has long been sought-after by scientists. But, so far, every attempt has failed, owing mainly to the risk of significant side-effects or concerns over long-term impacts on fertility.

The problem is a harder nut to crack than the creation of the female pill because unlike a woman's ovaries, which contain at birth all of the eggs she will ever need, sperm are made continuously throughout life.

Interfering with their production could therefore carry genetic or other risks for future offspring. Instead, a study published this week proposes an alternative approach: targeting the process that carries sperm out of the testes.

Writing in PNAS, Monash University scientist Carl White and his colleagues have switched off - in experimental mice - two genes encoding chemical receptors called P2X1 and the alpha 1a adrenoceptor.

These are expressed on the smooth muscle cells that line the vas deferens, the muscular tubes that connect the testes to the urethra so sperm can leave the body. Waves of nerve impulses triggered by sexual activity are communicated to these muscles thorough their P2X1- and alpha 1a adreno- receptors.

This provokes the muscles to produce peristaltic responses that propel sperm along. But male mice in which these genes had been deactivated, despite multiple successful matings, were unable to father offspring.

Their sperm, however, remained healthy and viable and the team were able to use it to do the equivalent of mouse IVF, fertilising eggs in vitro to produce heathy pups.

Although no one would advocate deactivating genes in a human for contraceptive purposes, according to the Monash team, it should be possible to use drugs to mimic the effects seen in the mice.

Encouragingly, there are already drugs available to block alpha1 adrenoceptors, although none are yet available to block P2X1 receptors, which the researchers think might take up to ten years.

Another problem with the present approach is that these chemical receptors are not exclusively active in the testes and are instead employed throughout the body where they help to control blood pressure and heart rate among other things.

A therapy targeting this system might therefore have a range of undesired systemic side effects. That said, the experimental animals showed few if any consequences, suggesting that a male contraceptive pill might be under a decade away...

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