Naked Mole-Rats: Scent of Success

Max Delbrück Center for Molecular Medicine in the Helmholtz Association

Imagine the following scenario: A head of state enters a room and emits a scent that prevents potential rivals from even considering challenging them. What's more, they remain calm and focused on their tasks. It may sound like a dystopian fantasy, but in naked mole-rat societies — it's a way of life.

An international team led by Dr. Gary Lewin, Group Leader of the Molecular Physiology of Somatosensory Perception lab at the Max Delbrück Center in Berlin, has discovered that the queens of naked mole-rat colonies release a volatile compound called isopropyl myristate, which induces temporary infertility in all other females in the colony.

"It works even when the queen is absent and the animals are exposed only to the scent," says Dr. Mohammed Khallaf from the Lewin lab and first author of the study. The research, which includes groups from Berlin, Frankfurt, Jena, Munich, and Paris, as well as collaborators in Egypt, South Africa, Tanzania, the Czech Republic, and the United States, was published in Nature.

Odorless to humans, not to naked mole-rats

For roughly 25 years, Lewin has studied the biology of naked mole-rats, a mammal native to Africa that is of considerable medical interest. The rodents — about 450 of which currently live at the Max Delbrück Center in tunnel systems modeled after their natural habitat — have exceptionally long lifespans, rarely develop cancer, and experience little pain. They are also among the very few eusocial mammal species that live in highly organized colonies, similar to those of bees or ants. A single breeding queen sits at the top of the hierarchy, while numerous infertile workers cooperate to gather food, raise young, and perform other tasks that benefit the colony.

"For this study, we wanted to understand the biological mechanisms that allow the queen to maintain her exclusive reproductive status," says Lewin. "We suspected that scent cues might play an important role, as they do in insects, particularly because we had already found that naked mole-rats use smell to distinguish members of their own colony from those from foreign colonies."

The researchers used mass spectrometry to characterize volatile compounds emitted exclusively by queens. They identified a familiar chemical: isopropyl myristate, which is commonly used in cosmetics as a solvent and moisturizing agent. It is odorless to humans, but turns out to be a very powerful compound in naked mole-rats.

"Using electrophysiological techniques and functional ultrasound imaging, which measures blood flow and thus activity in specific brain regions, we showed that their olfactory receptors detect the compound and that the resulting signals are processed in the brain's olfactory centers," explains Khallaf. "Higher-ranking animals also avoid the scent when given the opportunity, likely because it reminds them of the queen's dominance."

The queen odor alters hormone levels

When a naked mole-rat queen dies or is removed from the colony, fierce fights and new mating behaviors emerge within days. Once the first female becomes pregnant, she assumes the role of queen and stability returns. "In our experiments, however, we found that the queen's physical presence is not essential for maintaining harmony in the colony," says Lewin. "Simply spraying isopropyl myristate into the colony each day was enough." However, without the queen's odor, conflicts quickly resumed.

The compound had similar effects in pairs of animals. "If you place a female and a male from the same colony together in a cage, they become sexually active after a few days," says Khallaf. "That does not happen if they are exposed on a daily basis to bedding carrying the queen's scent. Remarkably, sexual interest also did not emerge when we applied isopropyl myristate directly to their cage each day."

Further experiments revealed that isopropyl myristate increases levels of prolactin, a hormone that reduces fertility in mammals. At the same time, it keeps levels of the fertility-promoting hormone progesterone low. "Together, these findings explain why naked mole-rats exposed to the queen's scent do not reproduce," explains Lewin.

Different species, similar strategies

The researchers also showed that queens produce isopropyl myristate only during pregnancy. "When a queen can no longer reproduce, progesterone levels rise in the other animals and prolactin levels fall," says Lewin. "At that point, succession struggles within the colony begin again."

"The idea that a single scent can maintain peace and prevent violence may sound like science fiction," says Khallaf. "In the world of naked mole-rats, it is reality." The team was surprised that such a complex social system appears to be regulated by a single chemical signal rather than a cocktail of pheromones, which is typically the case in insects, he adds. "Apparently, evolution likes to fall back on tried-and-true — and sometimes simplified — strategies, even across radically different species."

Max Delbrück Center

The Max Delbrück Center for Molecular Medicine in the Helmholtz Association aims to transform tomorrow's medicine through our discoveries of today. At locations in Berlin-Buch, Berlin-Mitte, Heidelberg and Mannheim, our researchers harness interdisciplinary collaboration to decipher the complexities of disease at the systems level – from molecules and cells to organs and the entire organism. Through academic, clinical, and industry partnerships, as well as global networks, we strive to translate biological discoveries into applications that enable the early detection of deviations from health, personalize treatment, and ultimately prevent disease. First founded in 1992, the Max Delbrück Center today inspires and nurtures a diverse talent pool of 1,800 people from over 70 countries. We are 90 percent

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