The essence of male scent promotes female puberty and estrus

Abstract Pheromones are chemical signals that trigger a response in another member of the same species. In mice, it has been shown that exposure of females to male pheromones leads to puberty advance and estrus induction. In particular, these effects can be triggered by conspecific male urine, suggesting that they are related to the chemical composition of this stimulus. Although these phenomena were among the earliest known examples of pheromonal actions, the identities of these chemical signals remain mysterious. Here we identified two small molecules in male urine, termed Calin319 and Calin381 that accounted for much of the vomeronasal neuronal response to male urine and were sufficient and necessary to advance juvenile female puberty and induce female estrus. Besides acting as a primer pheromone, a blend of these two male compounds also acts as a releaser pheromone that resulted in increased investigatory behavior by female mice. These findings demonstrate that Calin319 and Calin381 are crucial male pheromones that regulate female reproductive behavior in mice. This study resolves the long-standing mystery of the molecular code of male urinary chemicals that control female gonadal function.