Short-term rapamycin treatment increases ovarian lifespan inￂ young and middle-aged female mice

Summary Although age-related ovarian failure in female mammals cannot be reversed, recent strategies have focused on improving reproductive capacity with age, and rapamycin is one such intervention that has shown a potential for preserving the ovarian follicle pool and preventing premature ovarian f...

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Bibliographic Details
Published in:Aging cell 2017-08, Vol.16 (4), p.825
Main Authors: Dou, Xiaowei, Sun, Yan, Li, Jiazhao, Zhang, Jing, Hao, Dandan, Liu, Wenwen, Wu, Rui, Kong, Feifei, Peng, Xiaoxu, Li, Jing
Format: Article
Language:English
Subjects:
Age
Animal models
Data processing
Fertility
Follicles
Life span
Mating
Menopause
Middle age
Ovulation
Preservation
Rapamycin
Reproductive status
Rodents
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Summary:Summary Although age-related ovarian failure in female mammals cannot be reversed, recent strategies have focused on improving reproductive capacity with age, and rapamycin is one such intervention that has shown a potential for preserving the ovarian follicle pool and preventing premature ovarian failure. However, the application is limited because of its detrimental effects on follicular development and ovulation during long-term treatment. Herein, we shortened the rapamycin administration to 2 weeks and applied the protocol to both young (8 weeks) and middle-aged (8 months) mouse models. Results showed disturbances in ovarian function during and shortly after treatment; however, all the treated animals returned to normal fertility 2 months later. Following natural mating, we observed prolongation of ovarian lifespan in both mouse models, with the most prominent effect occurring in mice older than 12 months. The effects of transient rapamycin treatment on ovarian lifespan were reflected in the preservation of primordial follicles, increases in oocyte quality, and improvement in the ovarian microenvironment. These data indicate that short-term rapamycin treatment exhibits persistent effects on prolonging ovarian lifespan no matter the age at initiation of treatment. In order not to disturb fertility in young adults, investigators should in the future consider applying the protocol later in life so as to delay menopause in women, and at the same time increase ovarian lifespan.
ISSN:1474-9718
1474-9726
DOI:10.1111/acel.12617