On-demand male contraception via acute inhibition of soluble adenylyl cyclase.

Nearly half of all pregnancies are unintended; thus, existing family planning options are inadequate. For men, the only choices are condoms and vasectomy, and most current efforts to develop new contraceptives for men impact sperm development, meaning that contraception requires months of continuous pretreatment. Here, we provide proof-of-concept for an innovative strategy for on-demand contraception, where a man would take a birth control pill shortly before sex, only as needed. Soluble adenylyl cyclase (sAC) is essential for sperm motility and maturation. We show a single dose of a safe, acutely-acting sAC inhibitor with long residence time renders male mice temporarily infertile. Mice exhibit normal mating behavior, and full fertility returns the next day. These studies define sAC inhibitors as leads for on-demand contraceptives for men, and they provide in vivo proof-of-concept for previously untested paradigms in contraception; on-demand contraception after just a single dose and pharmacological contraception for men. Half of all pregnancies are unintended; thus, existing family planning options are inadequate. This proof-of-concept study validates an on-demand contraception strategy for men, showing high effectiveness in quickly and temporarily reducing male fertility in mice.

近一半的怀孕是意外的；因此，现有的计划生育选择是不足的。对于男性来说，唯一的选择是避孕套和输精管结扎术，而且目前大多数开发男性新型避孕药的努力都影响精子发育，这意味着避孕需要数月的持续预处理。在此，我们为一种按需避孕的创新策略提供了概念验证，即男性只需在性行为前不久按需服用避孕药。可溶性腺苷酸环化酶（sAC）对精子的活力和成熟至关重要。我们发现，单剂量的一种安全、速效且作用持久的sAC抑制剂可使雄性小鼠暂时不育。小鼠表现出正常的交配行为，且第二天生育能力完全恢复。这些研究确定sAC抑制剂可作为男性按需避孕药的先导物，并且它们为避孕中先前未经测试的模式提供了体内概念验证；即单剂量后的按需避孕以及男性的药物避孕。 一半的怀孕是意外的；因此，现有的计划生育选择是不足的。这项概念验证研究验证了一种男性按需避孕策略，表明在快速且暂时降低小鼠雄性生育能力方面具有高效性。