Frisky male mice find youngsters’ tears a turn-off

Pheromone in tears keeps males from trying to mate with immature mice.

"You smell like you've been crying." Credit: UCSD

Like humans, animals shed tears; there are reports of crying wolves, rats, gorillas, and elephants. But as far as we know, it isn’t out of sadness, frustration, or empathy. Instead, tears keep animals’ eyes moist and comfortable, and they help fight infection in and around the eyes. But tears also play an important role in animals’ behavior, according to a new study in this week’s issue of Nature. An international group of researchers has found that a chemical compound in mouse tears actually helps dictate sexual behavior.

The first part of the study was largely exploratory. By combing through the mouse genome, the researchers identified several genes that could produce potential pheromones. They were looking for any compounds that were expressed differently in mice of various ages, sexes, or physiological states in order to expand on what we know about how pheromones affect social interactions. One compound called ESP22 looked particularly promising: it was age dependent, with mice between two and three weeks of age showing the highest levels of expression.

ESP22 has another interesting quality as well. It is produced by a specialized set of cells in the lacrimal gland and then released into a mouse’s tears. In case you aren’t up to date on the latest research involving crying mice and sex, here’s a quick primer. Apparently, tears may play a significant role in mouse sex. In 2005, scientists identified a pheromone found in the tears of male mice that seemed to be involved in sexual behavior. A few years later, they found that this pheromone, called ESP1, makes female mice more sexually receptive when males approach them to mate.

This new compound, ESP22, had the hallmarks of another tear-based pheromone: it’s secreted in the tears of just a small subset of mice. The researchers reasoned that perhaps this compound, too, plays a role in regulating sexual behavior.

To test this hypothesis, the researchers used a strain of knockout mice with impaired sensory systems. These mice had non-functioning vomeronasal organs, which are normally responsible for sensing pheromones. If ESP22 were a pheromone involved in sexual behavior, mice that couldn’t sense ESP22 would behave differently from those that could, at least when it came to sex.

The researchers found a definite peculiarity in the behavior of these mice. In essence, the knockouts were very interested in mating with juveniles, whereas normal mice showed almost no sexual interest in young mice. Knockout mice were more likely to mount juveniles and tended to mount them more often than normal mice did. Clearly, something was prohibiting the mice with non-functioning vomeronasal organs from recognizing that the young mice were not appropriate mating targets.

But was it ESP22? After all, the vomeronasal organ could be picking up any one of many pheromones. So the researchers used a second set of knockout mice: juveniles that didn’t produce any ESP22 at all. These young mice were also the subject of unwanted sexual advances by normal mice. But when the researchers painted synthetic ESP22 on them, the mounting behavior stopped.

Together, these findings suggest that ESP22 is a pheromone expressed in juvenile mice that affects sexual behavior via the vomeronasal system. Mating with young mice isn’t exactly adaptive, since mounting prepubescent juveniles is a waste of time and energy. ESP22 appears to suppress males’ advances toward juveniles, likely directing their time and attention to more appropriate targets instead.

The ultimate goal of this research is to understand the role of chemical compounds in human behavior, but we’re a long way from reaching that goal. Humans don’t appear to have functioning vomeronasal organs, and our sexual rituals are a bit different from those of rodents. But there is evidence that human tears contain chemicals that affect sexual behavior, and it’s likely that tear-based compounds may regulate human behavior in other areas as well. The hope is that identifying and learning about pheromones in other animals will help us understand how chemicals affect our own sensory systems, behavior, and fitness.

Nature, 2013. DOI: 10.1038/nature12579 (About DOIs).