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Small-Molecule Inhibitor Has Potential As Male Contraceptive

Last Updated: August 16, 2012.

 

In mice, JQ1 inhibits BRDT, reducing sperm count and motility; yields reversible contraception

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In mice, a selective, small-molecule inhibitor, JQ1, which targets the testis-specific member of the bromodomain and extraterminal subfamily of epigenetic reader proteins, BRDT, can cross the blood:testis barrier and cause complete and reversible contraception in mice, according to a study published online Aug. 16 in Cell.

THURSDAY, Aug. 16 (HealthDay News) -- In mice, a selective, small-molecule inhibitor, JQ1, which targets the testis-specific member of the bromodomain and extraterminal subfamily of epigenetic reader proteins, BRDT, can cross the blood:testis barrier and cause complete and reversible contraception in mice, according to a study published online Aug. 16 in Cell.

Martin M. Matzuk, M.D., Ph.D., of the Baylor College of Medicine in Houston, and colleagues conducted a study evaluating the inhibition of the testis-specific BRDT, which is essential for chromatin remodeling during spermatogenesis, by a selective small-molecule inhibitor JQ1.

The researchers found that JQ1 prevents recognition of acetylated histone H4 by BRDT. In male mice, JQ1 crossed the blood:testis boundary and reduced seminiferous tubule area, testis size, and spermatozoa number and motility, but did not affect hormone levels. The inhibitory effect, evident at the spermatocyte and round spermatid stages yielded complete and reversible contraception, although treated males still mated normally.

"Our studies provide pharmacologic validation of the amino-terminal bromodomain of BRDT as a target for male contraception," the authors write. "These data support JQ1 as the first contraceptive agent that selectively and reversibly targets the male germ cell."

Two of the institutions have filed patent applications on technologies relating to the study, which have been licensed to Tensha Therapeutics.

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