Male version of 'the pill' a step closer

23:59, Aug 16 2012
The pill
ONE FOR THE BOYS?: Researchers have found a compound that makes male mice infertile.

A version of ''the pill'' for men is a step closer thanks to new research.

A compound called JQ1, which was originally developed as a cancer therapy, can also cause reversible infertility in male mice without apparent side effects for the rodents or their offspring, researchers have found.

The compound isn't ready for testing in healthy men, but it offers a promising lead in the quest for an improved male contraceptive.

"I'm delighted to see a new potential approach," said reproductive biologist William Bremner of the University of Washington School of Medicine in Seattle, who was not involved in the study.

Scientists have struggled for decades to find ways to reversibly and safely block male fertility.

Bremner said several key challenges stood in the way: First, men generate millions of sperm per day compared to the typical single egg a woman produced each month. Second, there was a "blood-testis barrier" that blocks many blood-borne compounds from reaching the area where sperm were produced.

Finally, any potential drug had to be extremely safe and not cause any lasting genetic damage to sperm or their precursor cells.

JQ1 was originally developed as an anti-cancer agent, said James Bradner, a chemical biologist at Dana-Farber Cancer Institute in Boston and one of the paper's authors.

It was designed to inhibit a protein called BRD4, which helps regulate cell division and is known to be involved in a type of aggressive skin cancer.

Bradner has high hopes that BRD4 inhibitors such as JQ1 will become cancer therapies, but he and his colleagues knew that BRD4 was also closely related to a protein called BRDT, which helped control cell division in the testis.

So they collaborated with Martin Matzuk,  a Texan a reproductive biologist, to test JQ1 as a potential contraceptive in mice.

The researchers report that after 6 weeks of daily injections of JQ1 the animals' sperm counts were reduced by nearly 90 per cent.

Only 5 per cent of the remaining sperm were able to swim properly, compared with 85 per cent of sperm in control mice.

After 3 months of treatment, none of the mice were able to sire offspring, although their mating behaviour was otherwise normal.
The compound had no apparent effect on the production of testosterone or other hormones made by the testes.

The researchers also showed that the effect was reversible. A month or two after treatment stopped, all of the mice were again able to father as many pups as control mice, and the animals' testis size and sperm counts returned to normal levels between 1 and 3 months after treatment stopped.

The treatment caused no obvious side effects in the mice, and the offspring of the treated animals showed no abnormalities.

The compound appeared to target developing sperm both before and after meiosis, the special cell-division process that forms sperm and eggs, Matzuk said.

That means that there are fewer sperm precursor cells in the testis, and few of those go on to produce functional sperm.

Bradner, the father of 18-month-old twins, joked that he had been taking "a gram a day" of JQ1 recently. 

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