Salk scientists discover new target for reversible, non-hormonal oral male birth control without affecting libido

Good news! 

Men have been waiting for this to happen ever since the hormonal female birth control pill was developed in 1960! Will gender equality finally arrive!

"Surveys show most men in the United States are interested in using male contraceptives, yet their options remain limited to unreliable condoms or invasive vasectomies. Recent attempts to develop drugs that block sperm production, maturation, or fertilization have had limited success, providing incomplete protection or severe side effects. New approaches to male contraception are needed, but because sperm development is so complex, researchers have struggled to identify parts of the process that can be safely and effectively tinkered with. ..."

From the abstract:

"Significance

... Despite the pressing need for population control, male contraceptive options are limited. These rodent studies demonstrate reversible male contraception by targeting silencing mediator of retinoid and thyroid hormone receptors-retinoid acid receptor signaling to identify a non-hormonal approach to male contraception.

Abstract

Despite numerous female contraceptive options, nearly half of all pregnancies are unintended. Family planning choices for men are currently limited to unreliable condoms and invasive vasectomies with questionable reversibility. Here, we report the development of an oral contraceptive approach based on transcriptional disruption of cyclical gene expression patterns during spermatogenesis. Spermatogenesis involves a continuous series of self-renewal and differentiation programs of spermatogonial stem cells (SSCs) that is regulated by retinoic acid (RA)–dependent activation of receptors (RARs), which control target gene expression through association with corepressor proteins. We have found that the interaction between RAR and the corepressor silencing mediator of retinoid and thyroid hormone receptors (SMRT) is essential for spermatogenesis. In a genetically engineered mouse model that negates SMRT-RAR binding (SMRTmRID mice), the synchronized, cyclic expression of RAR-dependent genes along the seminiferous tubules is disrupted. Notably, the presence of an RA-resistant SSC population that survives RAR de-repression suggests that the infertility attributed to the loss of SMRT-mediated repression is reversible. Supporting this notion, we show that inhibiting the action of the SMRT complex with chronic, low-dose oral administration of a histone deacetylase inhibitor reversibly blocks spermatogenesis and fertility without affecting libido. This demonstration validates pharmacologic targeting of the SMRT repressor complex for non-hormonal male contraception."

Salk scientists discover new target for reversible, non-hormonal male birth control - Salk Institute for Biological Studies Oral administration of HDAC inhibitor blocked sperm production and fertility in mice without affecting libido

Targeting nuclear receptor corepressors for reversible male contraception (no public access)

Sperm, pictured inside the cross-sectioned tube of the epididymis, were not generated while mice took the HDAC inhibitor drug (top right), but after 60 days off the drug, spermatogenesis was recovered (bottom right). The left column shows sperm at the same time points in a mouse that did not receive the drug.