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Aging Cell. 2017 Aug;16(4):825-836. doi: 10.1111/acel.12617. Epub 2017 May 22.

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

Author information

1
State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.
2
College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang, 163319, China.

Abstract

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.

KEYWORDS:

aging; mTOR; ovary; rapamycin

PMID:
28544226
PMCID:
PMC5506398
DOI:
10.1111/acel.12617
[Indexed for MEDLINE]
Free PMC Article

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