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

Area of Science:

• Reproductive biology
• Gerontology
• Pharmacology

Background:

• Age-related ovarian failure is a significant concern in female mammals, impacting reproductive capacity.
• Rapamycin shows potential for preserving ovarian follicles but long-term use has detrimental effects.
• Previous studies highlighted rapamycin's benefits but were limited by side effects.

Purpose of the Study:

• To investigate the effects of short-term rapamycin administration on ovarian lifespan and reproductive capacity.
• To determine if a 2-week rapamycin protocol can prevent premature ovarian failure without compromising fertility.
• To evaluate the impact of transient rapamycin treatment across different age groups in mouse models.

Main Methods:

• A 2-week rapamycin treatment protocol was applied to young (8-week-old) and middle-aged (8-month-old) female mice.
• Ovarian function, fertility, and ovarian lifespan were monitored during and after treatment.
• Key indicators such as primordial follicle count, oocyte quality, and ovarian microenvironment were assessed.

Main Results:

• Transient rapamycin treatment caused temporary ovarian function disturbances but fertility was restored within 2 months.
• Ovarian lifespan was prolonged in both young and middle-aged mice, with significant effects in older mice (>12 months).
• Preservation of primordial follicles, enhanced oocyte quality, and improved ovarian microenvironment were observed.

Conclusions:

• Short-term rapamycin treatment effectively prolongs ovarian lifespan with persistent positive effects, regardless of treatment initiation age.
• This transient protocol offers a viable strategy to delay menopause and enhance reproductive potential in aging females.
• Future applications should consider later-life administration to maximize benefits for delaying menopause and extending ovarian lifespan.