Increased longevity of old infertile mice after allo-transplantation of young mice ovaries

Abstract

OBJECTIVE: Most mammalian species are destined to die when their reproductive life is finished. If the most important evolutionary role of the individual is to produce the next generation, then the extension of reproductive life and increased longevity might be selectively correlated.DESIGN: To investigate this hypothesis, a young donor ovary was transplanted into old infertile mice, and the resumption of the reproductive cycle and life span of the mice were examined.MATERIALS AND METHODS: Female C57BL/6J mice (CLEA Japan inc.) were maintained for more than 525 days until they ceased to exhibit estrus, as determined by histology of vaginal smears. In Experiment 1, both ovaries were removed from young female mice (∼140 days old) that were immunologically compatible with the recipients, and these two ovaries were orthotopically transplanted into each of six aged, infertile recipient mice (>525 days old). In Experiment 2, one ovary was removed from intact young mice and transplanted into each of eight aged mice just as in Experiment 1.RESULTS: In Experiment 1 and Experimental 2, resumption of estrous cycles was obtained in all aged mice (resumption rate 100%), and normal estrous cycles continued for more than 80-130 days after the resumption. All the recipients in both experiments 1 and 2 resumed the normal reproductive behavior of young mice. Aged recipients that received young ovaries lived for an average of 836 (Exp.1) and 915 (Exp.2) days. The lifespan of mice who received young ovaries was thus much longer than that of intact mice (636 days). There was a 31-44% increase in lifespan in mice who received a transplant of young donor ovaries.CONCLUSION: The results in the present study suggest that transplanted normal ovaries can function in old infertile mice, which then not only resume the reproductive behavior of young mice, but also extend their lifespan. These results in mice may suggest the possibility of preventing the reproductive functional disorder of aging women by transplantation of a normal ovary. OBJECTIVE: Most mammalian species are destined to die when their reproductive life is finished. If the most important evolutionary role of the individual is to produce the next generation, then the extension of reproductive life and increased longevity might be selectively correlated. DESIGN: To investigate this hypothesis, a young donor ovary was transplanted into old infertile mice, and the resumption of the reproductive cycle and life span of the mice were examined. MATERIALS AND METHODS: Female C57BL/6J mice (CLEA Japan inc.) were maintained for more than 525 days until they ceased to exhibit estrus, as determined by histology of vaginal smears. In Experiment 1, both ovaries were removed from young female mice (∼140 days old) that were immunologically compatible with the recipients, and these two ovaries were orthotopically transplanted into each of six aged, infertile recipient mice (>525 days old). In Experiment 2, one ovary was removed from intact young mice and transplanted into each of eight aged mice just as in Experiment 1. RESULTS: In Experiment 1 and Experimental 2, resumption of estrous cycles was obtained in all aged mice (resumption rate 100%), and normal estrous cycles continued for more than 80-130 days after the resumption. All the recipients in both experiments 1 and 2 resumed the normal reproductive behavior of young mice. Aged recipients that received young ovaries lived for an average of 836 (Exp.1) and 915 (Exp.2) days. The lifespan of mice who received young ovaries was thus much longer than that of intact mice (636 days). There was a 31-44% increase in lifespan in mice who received a transplant of young donor ovaries. CONCLUSION: The results in the present study suggest that transplanted normal ovaries can function in old infertile mice, which then not only resume the reproductive behavior of young mice, but also extend their lifespan. These results in mice may suggest the possibility of preventing the reproductive functional disorder of aging women by transplantation of a normal ovary.