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Sperm blocking study brings 'male pill' closer

“Researchers announce discovery of proteins that can be blocked to prevent the launch of sperm cells during ejaculation,” The Guardian reports. The paper explains that if drugs can be found that turn off these proteins, a male contraceptive pill could become a reality.

However, the news is based on a study on mice in a laboratory. In the study, the male mice were bred to have two genes that were “turned off”, preventing the production of two proteins associated with sperm ejaculation. 

The researchers found that the technique had a 100% contraceptive success rate, and that there were no negative effects on the sexual behaviour of the mice or their sperm function.

Currently, there is no male contraceptive pill available. Research in this area has faced many challenges. The main challenge is that for male contraception to work, it needs to suppress all of the sperm a man produces. In comparison, female contraception only needs to suppress one ovum to be effective.

This is no mean feat as men produce around 300 million sperm when they ejaculate, so this potential new technique shows promise. The challenge for researchers is to find drugs capable of disrupting the effects of these proteins that are also safe and cause no or minimal side effects.

Until then, men’s best option for safe and reliable contraception (and protection against STIs) is the condom.

Where did the story come from?

The study was carried out by researchers from Monash University in Australia and the University of Leicester in the UK. It was funded by the National Health and Medical Research Council (NHMRC) in Australia and the Wellcome Trust in the UK.

The study was published in the peer-reviewed journal Proceedings of the National Academy of Sciences (PNAS) on an open access basis, so it is free to read online or download.

The UK media reporting of the study was accurate, although it should have been made clearer that this is early stage research and that a male pill for human use is yet to be developed. 

Some of the media reporting also covered findings from a previous study about women’s attitudes to whether or not they trusted their partners to remember to take the male version of the pill. However, this is a separate issue that was not considered by researchers conducting the current study.

What kind of research was this?

This was a laboratory study carried out on genetically modified male mice. It investigated whether the deletion of two genes was effective for producing short-term male infertility by interfering with the transport of sperm during ejaculation.

The researchers also wanted to see whether depletion of the proteins produced by the genes had an effect on sexual function, as well as looking at the effect on the sperm itself and its ability to be fertile later on.

Currently, the only contraceptive methods available to men are:

  • condoms – a barrier form of contraception that stops sperm from reaching and fertilising an egg
  • vasectomy – a minor surgical procedure that stops sperm being ejaculated

The issue with vasectomies is that they are often irreversible. If a reversal is carried out within 10 years of your vasectomy, the success rate is about 55%. This falls to 25% if the reversal is carried out more than 10 years after the procedure is performed.

What did the research involve?

In the laboratory, researchers genetically modified a group of male mice. These mice were bred not to have genes coding for α1A-adrenergic G protein-coupled receptors (adrenoreceptors) and P2X1-purinoceptor ligand gated ion channels (two types of proteins). The deletion of these specific genes was carried out so that sperm travel would be blocked during ejaculation.

The genetically modified male mice were then mated with normal female mice, and the female mice were assessed to see if they became pregnant.

The male mice also had their blood pressure and heart rate assessed, and their sperm underwent laboratory evaluation. Following this, sperm extracted from some of the male mice was injected into female eggs to see if the genetic deletion had an effect on whether the sperm were able to produce offspring.

The male mice were also compared with another group of male mice who had also been genetically modified, but this time they were only missing one of the two genes at a time.

What were the basic results?

For the 17 genetically modified male test mice, the researchers recorded 29 matings with female mice. No pregnancies occurred from any of these matings, which was interpreted as 100% infertility for the male test mice – this is what the research set out to achieve.

The male mice were reported to show normal sexual behaviour and function, and the researchers say the infertility was caused by a lack of sperm being ejaculated rather than dysfunctional sperm, also a positive finding.

Sperm extracted from three genetically modified test mice was able to fertilise eggs and produced normal baby mice following implantation, so the sperm of these mice was considered to not be altered by the depletion of the two genes.

How did the researchers interpret the results?

The researchers conclude that the genetic modification of male mice produced 100% infertility without effects on sexual behaviour or function. They say that sperm from these mice were capable of producing normal offspring following sperm injection and implantation of fertilised eggs into female mice.

The researchers say this method of male contraception appears free of major physiological and behavioural side effects.

In addition, they say the results “provide conclusive proof that pharmacological antagonism [using drugs to block the action] of the P2X1-purinoceptor and α1A-adrenoceptor provides a safe and effective therapeutic target for a non-hormonal, readily reversible male contraceptive.”

Conclusion

This laboratory study has investigated the effects on male fertility of a blocked ejaculation process following the depletion of two genes in a group of genetically modified mice.

As the researchers say, there is a need for different approaches to male contraception because most strategies have so far focused on hormonal approaches that produce dysfunctional sperm. The researchers say these often have intolerable side effects, such as affecting male sexual activity or causing long-term irreversible effects on infertility.

This laboratory study demonstrated that 100% male infertility was achieved among a group of genetically modified mice, with no negative effects on sexual behaviours or sperm function.

The researchers say the same effects could be achieved using oral drugs. This is where the findings become more relevant to humans. The researchers point that one of the two targets, the α1A-adrenoceptor, already has a drug that selectively inhibits its action.

This group of drugs – alpha blockers, such as Tamsulosin – are taken orally and are currently licensed for the treatment of benign prostate hyperplasia (non-cancerous swelling of the prostate gland). However, although alpha blockers have the same target, they are not contraceptive pills and have various cautions for their use, as well as associated side effects, one of which is erectile dysfunction – not ideal in a contraceptive.

Therefore, it should not be wrongly assumed that we are already halfway there and there is already a pill that can work as a male contraceptive, as further development of drugs targeting the α1A-adrenoceptor is needed. A drug for the second target protein (P2X1-purinoceptor) would have to be developed from scratch, which may take longer.

The researchers voiced concerns that using drugs to inhibit these two target proteins may have side effects for the heart and blood vessels. Of note, low blood pressure (hypotension) is one of the main side effects of the alpha blockers currently used to treat benign prostate hyperplasia. While no sign of this was found in mice, this would need close attention if it were ever tested on humans.

This was early stage exploratory research. So far, this research has only been tested in mice and the same tests have not been performed in humans. Further research is needed to see if a male pill would be effective and safe for use, and it’s likely this is some way off.

Until then, your best option would be the humble condom: a low-tech but highly effective contraceptive method when used correctly. 

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