Short-term rapamycin treatment increases ovarian lifespan in young and middle-aged female mice.
Short-term rapamycin treatment increases ovarian lifespan in young and middle-aged female mice.
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作者：
Dou X;Sun Y;Li J;Zhang J;Hao D;Liu W;Wu R;Kong F;Peng X;Li J
尽管雌性哺乳动物中与年龄相关的卵巢衰竭无法逆转，但最近的策略集中在随着年龄的增长提高生殖能力，雷帕霉素就是这样一种干预措施，它显示出保护卵泡池和预防卵巢早衰的潜力。然而，由于其在长期治疗期间对卵泡发育和排卵的不利影响，其应用受到限制。在此，我们将雷帕霉素给药缩短至2周，并将该方案应用于年轻（8周）和中年（8个月）小鼠模型。结果显示给药期间和给药后不久卵巢功能紊乱;然而，所有给药动物在2个月后恢复正常生育能力。在自然交配后，我们观察到两种小鼠模型的卵巢寿命延长，其中最突出的效果发生在12个月以上的小鼠中。瞬时雷帕霉素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和卵巢微环境的改善。这些数据表明，短期雷帕霉素治疗对延长卵巢寿命表现出持续作用，无论开始治疗时的年龄如何。为了不干扰年轻人的生育能力，研究人员将来应该考虑在以后的生活中应用该方案，以延迟女性的绝经期，同时增加卵巢寿命。
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.
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影响因子：
9.8
作者：
Medvedik O;Lamming DW;Kim KD;Sinclair DA
通讯作者：
Sinclair DA
DOI：
10.1530/jrf.0.0210081
发表时间：
1970-01-01
期刊：
JOURNAL OF REPRODUCTION AND FERTILITY
影响因子：
--
作者：
PEDERSEN, T
通讯作者：
PEDERSEN, T
影响因子：
13.3
作者：
May-Panloup, Pascale;Boucret, Lisa;Reynier, Pascal
通讯作者：
Reynier, Pascal
影响因子：
29
作者：
Bjedov I;Toivonen JM;Kerr F;Slack C;Jacobson J;Foley A;Partridge L
通讯作者：
Partridge L
影响因子：
4.5
作者：
Grabowska W;Sikora E;Bielak-Zmijewska A
通讯作者：
Bielak-Zmijewska A