Scientists have found a new method of interrupting sperm production, which is both non-hormonal and reversible.
The researchers demonstrate that treating male mice with an existing class of drugs, HDAC (histone deacetylase) inhibitors, can interrupt the function of this protein complex and block fertility without affecting libido.
“Most experimental male birth control drugs use a hammer approach to blocking sperm production, but ours is much more subtle,” said senior author Ronald Evans, Director of the Gene Expression Laboratory at the Salk Institute for Biological Studies. “This makes it a promising therapeutic approach, which we hope to see in development for human clinical trials soon.”
Salk scientists found that for this to work in order to produce mature sperm, retinoic acid receptors must bind with silencing mediator of retinoid and thyroid (SMRT) hormone receptors. SMRT then recruits HDACs, and goes on to synchronise the expression of genes that produce sperm.
The researchers looked at a line of genetically engineered mice that had previously been developed in the lab, in which the SMRT protein was mutated and could no longer bind to retinoic acid receptors. Without this SMRT-retinoic acid receptor interaction, the mice were not able to produce mature sperm. However, they displayed normal testosterone levels and mounting behaviour.
The researchers then treated normal mice with MS-275, an oral HDAC inhibitor. By blocking the activity of the SMRT-retinoic acid receptor-HDAC complex, the drug successfully stopped sperm production without producing obvious side effects.
Within 60 days of going off the pill, the animals’ fertility was completely restored, and all subsequent offspring were developmentally healthy.
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