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Male pill on horizon

9 December 2013
Appeared in BioNews 734

A reversible way of stopping sperm cells being ejaculated has been identified in mice. The research could pave the way for the development of a male contraceptive pill.

The researchers at Monash University, Australia, and the University of Leicester, UK, engineered male mice to lack two proteins - P2X1-purinoreceptors and alpha1A-adrenoreceptors. Together these proteins enable sperm cells to travel from the testes to the penis through a muscular tube called the vas deferens. Deletion of these proteins means that sperm remain in the testes upon ejaculation.

Study lead author Dr Sabatino Ventura of Monash University told the BBC: 'The sperm stay in the storage site so when the mice ejaculate there's no sperm and they are infertile'.

When the genetically-modified male mice were allowed to mate with female mice, no pregnancies resulted, meaning they were infertile. However, the male mice still showed normal sexual behaviour, which is an important requirement for a male contraceptive. The males also had normal sperm and were able to father offspring after their sperm was extracted and used to fertilise eggs in vitro.

Currently, there is no male contraceptive pill available and studies to date have focused on producing dysfunctional sperm that are unable to fertilise the egg. However, these methods can have serious side effects such as long term effects on fertility and sexual function. An advantage of the new approach is that sperm remain functional while sperm transport is blocked.

The next challenge will be to find a pair of drugs that can block these two proteins in humans. Adrenoreceptor-blocking drugs are already used to treat prostate hyperplasia - a benign swelling of the prostate gland. However, a purinoreceptor blocking drug has yet to be developed and this process could take years.

The two proteins that were targeted also have a role in controlling blood vessels so blocking them could have side effects on blood pressure or heart rate. Researchers only observed a very slight drop in blood pressure in the engineered mice but this would need to be carefully monitored if this approach was tested in humans.

Dr Allan Pacey, senior lecturer in andrology at the University of Sheffield, told the BBC: 'It's a good idea; they need to get on with it and see what it does in people'.

The study was published in the journal Proceedings of the National Academy of Sciences.
Male contraception via simultaneous knockout of α1A-adrenoceptors and P2X1-purinoceptors in mice
Proceedings of the National Academy of Sciences (PNAS) |  3 December 2013
Male contraceptive pill 'a step closer'
The Guardian (Press Association) |  2 December 2013
Male pill keeps sperm 'in storage'
BBC News |  3 December 2013
Sperm blocking study brings 'male pill' closer
NHS Choices |  3 December 2013
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