The approval of the combined oral contraceptive pill (or “the Pill”) in the 1960s ushered in a sexual revolution as women gained unprecedented control over their reproductive capabilities. But despite much research, the development of a male contraceptive pill has proven more elusive. Researchers at the Dana-Farber Cancer Institute and Baylor College of Medicine have now discovered that a small molecule compound can produce reversible birth control in mice, thereby showing promise as a lead compound for the development of a reversible male contraceptive.
The compound, called JQ1, disrupts the process by which sperm develop to become mature sperm by penetrating the blood-testis boundary. This results in a decrease in the number and quality of sperm, which is reversed when JQ1 was discontinued. The team’s study found the compound didn’t affect testosterone production, mating behavior, or the health of offspring conceived after JQ1 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, MD, the paper's senior author.
JQ1, which is named after Jun Qi, PhD, the lead chemist in Bradner’s lab, was originally synthesized at Dana-Farber to block a cancer-causing gene called BRD4. It has proven effective in models of lung cancer and in several blood cancers including leukemia and multiple myeloma. A group at Columbia University led by Dr. Debra J. Wolgemuth (who is also working on developing a male contraceptive pill) then revealed that mice lacking in BRDT were infertile.
This prompted further investigation that revealed that JQ1 blocks the normal process by which sperm are made by binding to a pocket of bromodomain testis-specific protein (BRDT), which is involved in the chromatin remodeling process during the generation of sperm in the testis.
Using JQ1 supplied by Bradner, Martin Matzuk, MD, PhD, of the Baylor College of Medicine and his team injected mice with the compound in solution and found that mice that received JQ1 had lower sperm counts, and their sperm were less mobile than those of mice who had not received the molecule. This rendered the JQ1-treated mice infertile.
"These findings suggest that a reversible, oral male contraceptive may be possible," said Bradner, who is also on faculty at Harvard Medical School and the Broad Institute. "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."
The Dana-Farber Cancer Institute and Baylor College of Medicine researchers’ paper appears in the journal Cell.
Bradner explains the research in the video below.
Source: Dana-Farber Cancer Institute
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