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.
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.