'Male pill hope' after mice research

'Male contraceptive pill step closer after mice studies' explains BBC News.

The story is based on research into whether a newly developed compound - JQ1 – could be be an effective method of contraception in male mice.

JQ1 (originally developed as a potential treatment for cancer) blocks a protein that is involved in sperm production.

Researchers found that male mice that were injected daily with JQ1 for a few months were not able to make female mice pregnant.

A couple of months after stopping treatment a recovery seemed to be complete and the mice were able to father healthy offspring.

The fact that JQ1 appears to be both an effective and reversible method of contraception means that it has considerable potential.

But it remains to be seen whether this or a similar drug could be developed that would be effective in men and not  cause serious side effects, such as long-term fertility problems
.
This is promising research, but there is a very long way to go before it could result in a contraceptive pill for men.

The claim that a reliable ‘male pill’ is just a ‘few years away’ has been made many times over the course of several decades.

 

Where did the story come from?

The study was carried out by researchers from Baylor College of Medicine, Houston, and other institutions in the US and Canada. The study received various sources of funding including Eunice Kennedy Shriver NICHD/NIH, an Alkek Award for Pilot Projects in Experimental Therapeutics, and a grant from the Fidelity Foundation.
The study was published in the peer-reviewed scientific journal: Cell.

The BBC News gives accurate coverage of this animal research, but the Daily Mail does not make it particularly clear that the ‘tests’ they speak of were in mice and not men. The Daily Telegraph notes that this drug was initially developed to as a possible cancer treatment, but was found not to be effective.

 

What kind of research was this?

This was research in mice and investigated the possibility of a male contraceptive pill.

The researchers report that contraceptive pills for men have so far remained elusive, with the only drugs tested in trials to date being hormonal ones which target testosterone production.

The current researchers have taken a different approach in attempting to develop small molecules that target the proteins which are involved in sperm production. One such potential target was a protein called BRDT which is thought to play an important role in the production of sperm cells.

Previous studies have demonstrated that stopping the action of this protein could induce sterility in mice.

The current research investigates a drug called JQ1 which is known to block some of the effects of BRDT.

Biological processes in animals such as mice and in humans do have many similarities, and animal research is a valuable first step in studying the biological effects of a particular drug to give an idea of how they may work in humans. However, there are also differences, so results in animal studies may not reflect what will be seen in humans.

Still, there is a large gap between a drug tested in animals and one that is marketed for use in humans, with many steps in between.

The drug would first need to show sufficient safety and efficacy in animals before it could be tested in humans. It would then have to pass a range of human safety and efficacy tests before it could be licensed for use by the general public.

 

What did the research involve?

JQ1 was dissolved in a solution and then injected into the abdomen of male mice twice a day. A control group of male mice were injected with just the inactive solution without JQ1. Mice were weighed daily and fed as normal.

Mice were pre-treated with the injections for six weeks, and from then on caged continuously with females while continuing to receive injections for a further two months and at an increased dose in the second month. Each male was caged with two females.

Males that were successfully sterilised (did not make the females pregnant) after the two months of treatment were allowed to remain in the cage with the females, untreated, for a further seven months.

Conversely males that continued to produce offspring during the second month received a further month’s treatment at a higher dose, and then after the three months of treatment were also allowed to remain in the cage with the females, untreated, for a further seven months.

They also carried out a separate set of laboratory tests to examine the effects of JQ1 upon the males. A sample of treatment and control mice had their testes (the part of the male reproductive system that produces sperm) examined and had measures of sperm taken immediately after completion of JQ1 treatment. Another sample of mice was examined four months after stopping JQ1, to see if the effects were reversed.

 

What were the basic results?

For the mice that were allowed to live with the females during and after treatment with JQ1, they found that during treatment the mice still mated normally, but JQ1 had the expected contraceptive effect and the female mice did not become pregnant.

Assessment of mice in the subsequent months revealed that for the male mice that stopped treatment after two months, there was a restoration of fertility around month four. For those that received three months of treatment, there was a restoration of fertility around month six.

From the sample of mice examined immediately after JQ1 treatment they found that they had reduced size of testes, the area of the seminiferous tubules (where sperm are made) and reduced sperm number and motility (motility is the ability of sperm to ‘swim’ towards a female egg). It had no effect on male hormone levels. When they examined mice four months after stopping JQ1 treatment it revealed that their testes and sperm had returned to normal.

The fact that the contraceptive effects of JQ1 are reversible is significant as some previous attempts to produce a ‘male pill’ have proven unsuccessful as they caused permanent infertility.

Another significant factor was that the baby mice born after stopping JQ1 treatment were also all normal and healthy.

 

How did the researchers interpret the results?

The researchers conclude that they have developed a treatment, JQ1, which can block BRDT activity during sperm development, resulting in a reversible contraceptive effect in male mice.

 

Conclusion

This type of research is a valuable early step in trying to develop a contraceptive pill that could be used by men.

The mice experiments demonstrated that JQ1 seemed to have a reversible contraceptive effect, specifically the treatment reduced:

  • the size of the mouse testes
  • the area of the seminiferous tubules (where sperm are made)  
  • the number and motility of sperm 

The combination of these three effects appears to have prevented the mice from making the female mice pregnant.

Complete recovery appeared to have occurred a few months after stopping treatment.

Researchers hope that it may be possible to produce a drug that could target the same BRDT protein in men. However, the research is at a very early stage and many more steps will be needed to see whether it could be possible to develop this, or a similar drug for use in people, and whether it would have the same effects. Most importantly - given its effects in mice of reducing testis size and sperm number and motility – it would need to be ensured that the drug was actually safe for use and didn’t result in longer-term fertility problems, or have any other detrimental effects on the health of the men or their subsequent children.

As Professor Moira O'Bryan, the head of male infertility at Monash University in Australia, is quoted as saying in BBC news, “Although there is undoubtedly an urgent need for additional contraceptive options, the path between this paper and a new product is likely to be long.” 

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on twitter.

Matzuk M, McKeown M, Filippakopoulos P, et al. Small-Molecule Inhibition of BRDT for Male Contraception. Cell. Published online August 17 2012

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