Short‐term rapamycin treatment increases ovarian lifespan in?young and middle‐aged female mice

Xiaowei Dou; Yan Sun; Jiazhao Li; Jing Zhang; Dandan Hao; Wenwen Liu; Rui Wu; Feifei Kong; Xiaoxu Peng; Jing Li

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Short‐term rapamycin treatment increases ovarian lifespan in?young and middle‐aged female mice

机译：雷帕霉素短期治疗可延长雌性和中年雌性小鼠的卵巢寿命

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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.

机译：尽管雌性哺乳动物中与年龄有关的卵巢功能衰竭无法逆转，但最近的策略集中于随着年龄的增长提高生殖能力，雷帕霉素是一种这样的干预措施，已显示出保留卵巢卵泡库和预防卵巢早衰的潜力。但是，由于其在长期治疗期间对卵泡发育和排卵的有害作用，其应用受到限制。在这里，我们将雷帕霉素的给药时间缩短到2周，并将该方案应用于年轻（8周）和中年（8月）小鼠模型。结果显示，在治疗过程中和治疗后不久，卵巢功能出现紊乱。但是，所有接受治疗的动物在2个月后恢复了正常生育能力。自然交配后，我们在两种小鼠模型中均观察到卵巢寿命延长，其中最显着的影响发生在12个月以上的小鼠中。雷帕霉素短暂治疗对卵巢寿命的影响反映在原始卵泡的保存，卵母细胞质量的提高以及卵巢微环境的改善上。这些数据表明，无论治疗开始时的年龄如何，雷帕霉素短期治疗均能持续延长卵巢寿命。为了不干扰年轻人的生育能力，研究者将来应考虑在生活中后期应用该方案，以延缓妇女的更年期，同时延长卵巢寿命。

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《Aging cell.》 |2017年第4期|共12页
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Xiaowei Dou; Yan Sun; Jiazhao Li; Jing Zhang; Dandan Hao; Wenwen Liu; Rui Wu; Feifei Kong; Xiaoxu Peng; Jing Li;
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1. Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice [J] . Alessandro Bitto, Takashi K Ito, Victor V Pineda, eLife journal . 2016,第february期

机译：雷帕霉素的短暂治疗可增加中年小鼠的寿命和健康
2. Short-term treatment with rapamycin and dietary restriction have overlapping and distinctive effects in young mice [J] . The journals of gerontology.Series A. Biological sciences and medical sciences . 2013,第2期

机译：雷帕霉素和饮食限制的短期治疗对年轻小鼠具有重叠和独特的作用
3. Long-term dietary supplementation with a yang-invigorating Chinese herbal formula increases lifespan and mitigates age-associated declines in mitochondrial antioxidant status and functional ability of various tissues in male and female C57BL/6J mice. [J] . Ko KM, Chiu PY, Leung HY, Rejuvenation research . 2010,第2a3期

机译：长期饮食补充阳气中草药配方可延长寿命，并减轻与年龄相关的雄性和雌性C57BL / 6J小鼠线粒体抗氧化剂状态和各种组织功能能力的下降。
4. Effects of exercises on the myocardium in the female mice ldl-knockout subjected to deprivation of ovarian hormone [C] . Brianezi L., Neto W.K., Souza R.R., International Congress on Coronary Artery Disease . 2011

机译：锻炼对卵巢敲除剥夺卵巢激素的雌性小鼠LDL淘汰中的影响
5. Young Hematopoietic Stem Cells Ameliorate Age-Associated Phenotypes and Extend Lifespan in Mice [D] . Guderyon, Michael James 2019

机译：年轻的造血干细胞可改善小鼠的年龄相关表型并延长其寿命
6. Short‐term rapamycin treatment increases ovarian lifespan in young and middle‐aged female mice [O] . Xiaowei Dou, Yan Sun, Jiazhao Li, 2017

机译：雷帕霉素短期治疗可延长雌性和中年雌性小鼠的卵巢寿命
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Short‐term rapamycin treatment increases ovarian lifespan in?young and middle‐aged female mice

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