Postnatal Oogenesis Conveys Exceptional Fertility to Naked Mole-Rats

The naked mole-rat has an enviable existence. It has a long life (30 years or more), is highly resistant to cancer, and, now, new research has found that female naked mole-rats produce eggs throughout their lives, facilitating almost eternal fertility. The study, published in Nature Communications, sheds light on the processes behind naked mole-rat’s exceptional fertility, and discusses implications for human fertility drug development.

“Naked mole-rats are the weirdest mammals,” said lead author Miguel Brieño-Enríquez, M.D., Ph.D., from the University of Pittsburgh. “They’re the longest-lived rodent, they almost never get cancer, they don’t feel pain like other mammals, they live in underground colonies, and only the queen can have babies. But to me, the most amazing thing is that they never stop having babies—they don’t have a drop in fertility as they age. We want to understand how they do this.”

For most mammals, including humans and mice, females are born with a finite number of egg cells, which are produced in utero via oogenesis. Because this limited supply of egg cells depletes over time—some are released during ovulation, but most simply die—fertility declines with age. In contrast, naked mole-rat queens can breed right through old age, suggesting the rodents have special processes to preserve their ovarian reserve and avoid waning fertility.

“There are three possibilities for how they do this: They are born with a lot of egg cells, not as many of these cells die, or they continue to create more egg cells after birth,” said Brieño-Enríquez. “My favorite hypothesis is that they use a cocktail of all three.”

The researchers compared ovaries from naked mole-rats and mice across different stages of development. Despite their similar sizes, mice live four years at most and start to show a drop in fertility by nine months, whereas naked mole-rats have a life expectancy of 30 years or more.

They found that naked mole-rat females have exceptionally large numbers of egg cells compared to mice and that death rates of these cells were lower than in mice. For example, at 8 days old, a naked mole-rat female has on average 1.5 million egg cells, about 95 times more than mice of the same age.

Most remarkably, the study found that oogenesis happens postnatally in naked mole-rats. Egg precursor cells were actively dividing in 3-month-old animals, and these precursors were found in 10-year-old animals, suggesting that oogenesis could continue throughout their lives.

Naked mole-rats live in colonies of several dozen to hundreds of individuals. Like bees or ants, colony members divvy up tasks, including providing defense, digging tunnels, caring for young and collecting food. Only the single dominant female in a colony can breed, and she suppresses reproduction in other females to maintain her queenly status.

To learn more about this process, the researchers removed 3-year-old females from the colony to prompt reproductive activation and compared these new queens with subordinate females. They found that non-breeding subordinates had egg precursor cells in their ovaries, but the cells started dividing only after a transition to queen.

“This is important because if we can figure out how they’re able to do this, we might be able to develop new drug targets or techniques to help human health,” said Brieño-Enríquez. “Even though humans are living longer, menopause still happens at the same age. We hope to use what we are learning from the naked mole-rat to protect ovary function later in life and prolong fertility.”