A new study sheds light on why naked muscles have something akin to eternal fertility.
The findings were published in the journal Nature communicationsit could point to new treatments for humans.
“Naked muscles are the strangest mammals,” says lead author Miguel Brieño-Enríquez, an assistant professor at the Magee-Womens Research Institute and the Department of Obstetrics, Gynecology and Reproductive Sciences at the University of Pittsburgh School of Medicine. “They are the longest living 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 decline in fertility as they get older. We want to understand how they do this.”
For most mammals, including humans and mice, females are born with a finite number of eggs, which are produced in the uterus through a process called oogenesis. Because this limited supply of eggs is depleted over time—some are released at ovulation, but most simply die—fertility declines with age.
In contrast, naked lead queens can reproduce into old age, suggesting that rodents have special processes to maintain their ovarian reserve and avoid declining fertility.
“There are three possibilities for how they do this: They’re born with a lot of eggs, not as many of those cells die, or they keep making more eggs after they’re born,” says Brieño-Enríquez. “My favorite hypothesis is that they use a cocktail of all three.”
Sure enough, Brieño-Enríquez and colleagues found evidence for each of the three processes.
The researchers compared ovaries from naked mice and mice at different stages of development. Despite their similar sizes, mice live a maximum of four years and begin to show a decline in fertility at nine months, while naked mice have a life expectancy of 30 or more.
They found that nude female cetocytes have an extremely high number of eggs compared to mice, and that the death rates of these cells were lower than in mice. For example, at 8 days of age, a naked female mole-mouse has an average of 1.5 million eggs, about 95 times more than mice of the same age.
Most notably, the study found that oogenesis occurs postnatally in glabrous muscles. Oocyte 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.
“This finding is extraordinary,” says senior author Ned Place, a professor at Cornell University College of Veterinary Medicine. “It challenges the dogma established nearly 70 years ago that female mammals are endowed with a finite number of eggs before or shortly after birth, with no additions to the ovarian reserve thereafter.”
Naked mole rats live in colonies of several tens to hundreds of individuals. Like bees or ants, colony members undertake tasks such as providing defense, digging tunnels, caring for the young, and gathering food. Only the single dominant female in a colony can reproduce, and she suppresses reproduction in other females to maintain her queenship.
“Unlike bees or ants, a naked female rat is not born a queen,” explains Brieño-Enríquez. “When the queen dies or leaves the colony, subordinate females compete to take her place and become reproductively active. Every girl can be a queen.”
To learn more about this process, the researchers removed three-year-old females from the colony to induce reproductive activation and compared these new queens to subordinate females. They found that non-breeding subordinates had egg precursor cells in their ovaries, but the cells only started dividing after transitioning to the queen.
“This is important because if we understand how they can do this, we may be able to develop new drug targets or techniques to help human health,” says Brieño-Enríquez. “Even though people are living longer, menopause still happens at the same age. We hope to use what we learn from the naked mole to protect ovarian function later in life and prolong fertility.”
“But the ovary is more than a baby factory,” she continues. “Ovarian health affects cancer risk, heart health, and even lifespan. A better understanding of the ovary could help us find ways to improve overall health.”
Additional authors are from the University of Toronto. the University of Pittsburgh; the University of California, San Francisco; and Cornell University.
Funding came from the National Institutes of Health, the Natural Sciences and Engineering Research Council of Canada, an Ontario Early Investigator Award, a WM Keck Foundation Award, the Empire State Stem Cell Fund, and a Magee-Auxiliary Woman Scholar grant.
Source: University of Pittsburgh