The strange rodent that’s immune to cancer also holds the key to infertility

Women are living longer, but their reproductive cycles remain the same. From the age of 35, fertility drops at an accelerated rate, yet more women are trying to have children starting at this age, when the chances of success are lower. Among the many avenues of research to overcome this limitation of nature, some scientists see possibilities in the naked mole-rat, a rodent that lives in subterranean colonies in Kenya, Ethiopia, and Somalia – and now also in laboratories around the world because of scientific interest in their biological peculiarities.

Although it belongs to the same family as the mouse or the rat, which can live up to two and four years respectively, the naked mole-rat can reach 32 years of age. And they are fertile throughout their extremely long lives. Previous studies by researchers such as the biologist Vera Gorbunova have discovered how these animals produce much larger hyaluronic acid molecules than humans or mice, something that could explain, at least in part, why they are virtually immune to cancer. And they live much longer than one might expect. Traits like these have caught the attention of oncologists.

A team led by Miguel Brieño-Enríquez, from the University of Pittsburgh, has published a study in the journal Nature Communications in which the processes that allow these animals to maintain their fertility or even increase it over the years are explained. “In the laboratory we have a 17-year-old queen and her last litter was 27 pups. A one-year-old or two-year-old female can have a litter of eight,” says Brieño-Enríquez.

In this peculiar species of rodent, only one of the females in the colony is fertile, similar to what happens with bees or termites, but with a somewhat more meritocratic system, because the queen is not born so. When the incumbent dies or disappears, other females vie for the throne and the chance to reproduce until the next regime change.

In almost all mammals, including humans and mice, females are born with a number of oocytes (germ cells) that are produced while in their mother’s womb. A number of these oocytes develop into eggs, but most simply deteriorate and die. The Mexican researcher says that three possibilities were raised to explain the improved fertility of naked mole-rats: “One was that they were born with many oocytes, another that few of those they had at birth died and, finally, that the females continue to generate oocytes after birth.” The results of the study indicate that there is something of all three.

This does not mean that tomorrow there will be a magic pill to make people fertile for life, but it is progress

Miguel Brieño-Enríquez, University of Pittsburgh

The researchers compared, at different stages of development, the ovaries of naked mole-rats, which are fertile throughout their lives, with those of mice, which begin to lose fertility at nine months after birth. Among other findings, they observed that eight days after birth, naked mole-rats had 95 times more oocytes than mice of the same age; they also found that oocyte production was still possible in naked mole-rats 10 years after birth.

Another interesting aspect of these animals is that all the females can reproduce or not, depending on whether they have a queen above them or they are queens themselves. To understand the processes behind these changes, the study authors removed three-year-old females from the colony, making it possible for them to become fertile. Thus, they saw that the subordinates have the precursor cells of the egg cells in their ovaries, but they only began to divide when the females acquired the status of queen.

“This way we can take these cells and culture them to divide them in vitro and analyze the mechanisms that control them. We can see how to activate certain genes that have to do with protecting the quality of the eggs and the environment in which they live to protect the function of the ovaries,” says Brieño-Enríquez. “The most important thing about this is that we have observed that many of these genes are also found in humans, but deactivated or not as active as in these animals,” he adds. This, the researcher clarifies, “does not mean that tomorrow there will be a magic pill to make people fertile for life, but it is progress.”

The possibility of these genetic modifications to mimic the power of naked mole-rat ovaries, which is already being successfully tested in mice, would not only be of reproductive interest. “The ovary is also part of a system that protects the body from osteoporosis, cancer and mental illness, and that protection disappears when a woman reaches menopause. This work allows us to think about how to maintain the benefits of an active ovary for a much longer time,” says Brieño-Enríquez, who believes that this could be achieved with epigenetic modifications associated with the on-and-off activation of fertility observed in naked mole-rats.

Despite not having cancer and showing an unusual resistance to pain, naked mole-rats also die. Their immune system does not protect them from viral infections (some coronaviruses have killed off entire laboratory colonies) and there comes a time when their heart, like a machine programmed for obsolescence, simply stops beating. However, they remain one of the most interesting animals to understand the mysteries of longevity. As Brieño-Enríquez summarizes, “they may not win a beauty contest, because they don’t have a canonical type of beauty, but they definitely have won the contest of life, because they have all the defense mechanisms you can imagine to survive many things.”

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