Male contraceptive pill takes a step closer
US scientists discover a small molecule compound that decreases number and quality of sperm in mice
Scientists claim to be moving nearer to making oral birth control for men a reality after an early study revealed that a compound known as JQ1 reversibly inhibited fertility in male mice.
Researchers at Dana-Farber Cancer Institute and Baylor College of Medicine in the US say JQ1 can cross the blood-testis boundary, disrupt spermatogenesis and result in a decrease in the number and quality of sperm, without impairing testosterone production, mating behaviour, or the health of offspring conceived after its use.
‘Our findings demonstrate that, when given to rodents, this compound produces a rapid and reversible decrease in sperm count and mobility with profound effects on fertility,’ said Dana-Farber’s James Bradner, the paper’s senior author.
Martin Matzuk, of Baylor College of Medicine, is the paper’s first author.
JQ1 was originally synthesised to block BRD4, a cancer-causing gene. Named after the lead chemist, Jun Qi, in the Bradner laboratory, JQ1 has proven effective in models of lung cancer and in several blood cancers including leukaemia and multiple myeloma.
The Dana-Farber/Baylor collaboration started when Bradner told Matzuk that he was testing JQ1 as an inhibitor of a member of a family of bromodomain proteins, and he wanted to know whether it would have an effect on a spermatogenic-specific member of that family called BRDT.
This was based on earlier research from Debra Wolgemuth and her group at Columbia University, which revealed that mice lacking BRDT were infertile.
BRDT is involved in the chromatin remodelling process during the generation of sperm in the testis. It is ‘remodelled’ to give the proteins that regulate how genes act access to the genetic material. JQ1 subverts that process by binding to a pocket of BRDT that is necessary for chromatin remodelling to take place. In doing this, it blocks the normal process by which sperm are made, thereby reducing their production and quality.
‘These findings suggest that a reversible, oral male contraceptive may be possible,’ said Bradner.
‘While we will be conducting more research to see if we can build on our current findings, JQ1 shows initial promise as a lead compound for male contraception.’
Details of the study are published in the journal Cell.