Mechanisms and Evolutionary Advantages of Unlimited Reproductive Lifespans in Naked Mole-Rat Queens

The naked mole-rat ( Heterocephalus glaber ) defies mammalian norms with lifelong fertility and postnatal oogenesis. Unlike most mammals, which experience reproductive senescence due to depletion of a finite ovarian follicle pool, naked mole-rat queens maintain fertility for their entire 30+-year lifespan through multiple mechanisms, including postnatal oogenesis, an exceptionally large ovarian reserve, and maintenance of primordial germ cells into adulthood. This review explores the unique reproductive biology of naked mole-rats within the context of their eusocial lifestyle, examining how social suppression of reproduction in subordinates, the role of very-high-molecular-weight hyaluronan (vHMW-HA) in cancer resistance and tissue maintenance, and the maintenance of germline stem cell populations contribute to their extraordinary reproductive longevity. We discuss the evolutionary advantages of eusociality, mechanisms of reproductive suppression and activation, and the potential of naked mole-rats as a research model for understanding ovarian aging and developing fertility-preserving therapies in humans.