Most mammals, including humans, have a constantly dwindling supply of eggs, becoming less fertile with age. But naked mole rats can reproduce for their entire lives—and researchers may have uncovered the fascinating reason how.
Along with having an exceptionally large reserve of healthy egg cells in their ovaries, naked mole rats create new eggs after being born, according to a new study published in the journal Nature Communications. Humans, on the other hand, are likely born with all the eggs we will ever have.
Native to East Africa, naked mole rats have baffled scientists for decades. These wrinkly, communal-living rodents can live up to 37 years, handle extremely low-oxygen conditions, and do not get cancer, traits that are all being studied to develop new medicines and therapies.
Now, the secrets behind naked mole rats’ lifelong breeding abilities could offer clues to helping prolong human fertility, says study leader Miguel Brieño-Enríquez, a reproductive researcher at the University of Pittsburgh.
“Female reproduction and female aging are way understudied,” he says. “In our case, we want to [investigate] how the ovary is the key for aging, and protecting that is the main goal.”
An astonishing number of eggs
The exact age in which women experience a dip in fertility is hotly debated. However, most research shows that women's egg cells start to deteriorate around 40, and having a baby at this age can increase the risk of chromosomal abnormalities and other disorders. Around age 50, during menopause, a woman’s ovaries stop releasing eggs altogether. (Learn why many women are opting to freeze their eggs.)
But female naked mole rats can breed for their entire lives with no notable decline in the quality of their eggs. To test how this is possible, Brieño-Enríquez and colleagues removed the ovaries from six naked mole rats from their research colony at the University of Pittsburgh. Then, under a microscope, they analyzed these ovaries at different periods of development—from one to 90 days—and compared them with the ovaries of lab mice, an animal commonly used as a model for human reproduction.
The team used a variety of staining techniques and immunofluorescence—glowing markers that can track cells as they divide—to count the number of germ cells in each animal that will eventually divide into mature egg cells known as oocytes. On day five, they discovered an astonishing number of germ cells in the naked mole rats, vastly outnumbering those contained in the mice.
“To me, it was really exciting, but part of it was also intimidating,” says Ned Place, study senior author and reproductive biologist at the Cornell University College of Veterinary Medicine. “I was like, ‘Oh my gosh, somebody—that means me and my lab—is going to have to count all these cells.’”
Then, things got even weirder: When the scientists looked again three days later, they discovered that the naked mole rats’ ovaries had even more germ cells than when they last checked, meaning the rodents were creating new cells to add to their ovarian reserve. At eight days old, the naked mole rat females had on average 1.5 million eggs, roughly 95 times more than mice of the same age.
The researchers also found precursor egg cells in 10-year-old naked mole rats, suggesting that the creation of new eggs could continue well into their 20s and 30s. (Read how naked mole rats are immune to burning pain.)
Learning from royalty
Similar to bees, naked mole rats live in colonies, sometimes made up of hundreds of individuals, with just one breeding queen.
This dominant female suppresses the ability of other females to reproduce until her reign comes to an end. If a queen dies or is killed, the other females will fight for the throne, and the winner will become the new breeding female of the colony.
To test how this process affects fertility, the researchers created their own queens by removing several three-year-old, non-breeding females from their colony into a new area to activate their reproductive systems.
They found that these females already had primordial germ cells in their ovaries, but the cells only started dividing into eggs when they transitioned to a queen.
That means that this previously untapped reserve of cells could become viable eggs even after years of dormancy—a discovery that may offer clues to prevent declining fertility in women.
Helping women boost their fertility
“What they have shown in this paper really, really beautifully is that [naked mole rats] are perfect models for humans," says Gisela Helfer, a neuroendocrinology researcher who was not involved in the study.
For instance, scientists can study puberty in naked mole rats without having to perform surgery on their reproductive organs, as is required with mice.
“What we want to know is how the naked mole rats can keep their oocytes healthy and happy for that long,” adds Brieño-Enríquez. From there, researchers could eventually develop new drug targets or supplements to protect a woman’s existing egg cells. Even so, Brieño-Enríquez stresses this likely won’t result in some “magic pill" for infertility.
But he still believes we have a lot to learn from naked mole rats.
“I like weird things in general, and when it comes to an organism that is giving you so much room to play, work feels like a playground,” he says. “It is also a pain because whatever you expect to see, it's exactly backwards.”
