Pheromone in baby mouse tears makes females less interested in sex

The discovery may have applications for rodent control.

When mice aged between one and three weeks cry, they produce a pheromone that makes both mothers and virgin female mice more likely to reject male sexual advances. Scientists believe that by making the females around them less interested in sex, baby mice are able to reduce the competition for resources. The pheromone is called exocrine gland-secreting peptide 22 (ESP22), and researchers say it could one day be added to drinking water to control rodent populations.

We spoke to Professor Kazushige Touhara from the University of Tokyo about the work.

ResearchGate: What motivated this study?

Kazushige Touhara: In 2013, we published a paper describing that ESP22 from infants suppressed male sexual behavior. And subsequently, became interested in its effects on females.

RG: Can you tell us how it makes female mice reject male sexual advances?

Touhara: An ESP22-stimulated female mouse shows at least one of the following postures: standing, crouching down, keeping their limb tight, or turning their body to inhibit insertion when male mice tried to mount onto female mice. We call this behavior “rejection.” This behavior is related to a specific neural pathway.

In mice, a pheromone in juvenile tears causes females to reject male sexual advances. Image by Kazushige Touhara CC-BY-SA.

RG: How do you see it being used for rodent control?

Touhara: ESP22 exposure led to late births and a decrease in the ratio of females with pups, suggesting that it acts as a reproductive suppression signal. Therefore, EPS22 could be applied to the drinking water to suppress the mouse population. But we have not tried a field study yet.

RG: Are there any dangers that it could affect other animals?

Touhara: Pheromones are species specific. ESP22 is a mouse pheromone that does not exist in other animals, and thus, ESP22 does not affect other animals. In addition, ESP22 is a protein and not a chemical that is sometimes hazardous.

RG: Do you think the pheromone could have any other applications outside of pest control?

Touhara: We have observed that ESP22 attracts lactating mothers, which may help keep the mother around ESP22-secreting juveniles in the nest. Together with ESP1, which enhances sexual behavior, we may be able to apply these pheromones for maintaining laboratory mice that often are hard to breed or show less maternal behavior.

RG: Why do you think ESP22 has this effect?

Touhara: We think that ESP22-mediated sexual suppression could be beneficial for females in natural environments, as the presence of growing juveniles is a sign that there might resource competition in the future and potential overpopulation. For juvenile mice, it could ensure fewer competitors and a resource-rich environment.

RG: What’s next for your research?

Touhara: ESP22 cannot be chemically synthesized and has to be prepared, for example, in bacteria, which is time and labor intensive. We are now in the process of identifying an active fragment within ESP22 that can be easily prepared and utilized.

We also demonstrated that the ESP1-dependent sexual behavior was fully suppressed by ESP22. We are interested in how the opposing effects (sexual enhancement by ESP1 and suppression by ESP22) are regulated at a circuit level in the brain.