Exercise preserved the primordial follicle reserve in mice, including early structures that contain immature oocytes
Exercise preserved the primordial follicle reserve in mice, including early structures that contain immature oocytes
On 14 August, Nature Aging published a study that compared data on physical activity and age at menopause in women with experiments in mice. In the mouse experiments, the authors linked preservation of the follicle reserve to adiponectin, a protein hormone, and tested this pathway using AdipoRon, a compound that activates adiponectin receptors.
The ovaries contain a finite reserve of primordial follicles from birth. These are early structures that contain immature oocytes. Once a follicle begins to grow, it permanently leaves this reserve. The rate at which follicles begin growing therefore determines how quickly the ovarian reserve is depleted.
In two cross-sectional studies of women, participants who had not yet reached menopause reported higher levels of physical activity. Among 100 703 postmenopausal participants in the UK Biobank, higher activity was associated with a later age at menopause. To determine whether exercise affects the follicle reserve itself, the authors placed mice on the same running regimen.
Eight-week-old female mice ran on a treadmill for 30 minutes, five days a week, for one month. Control animals spent the same amount of time on a stationary treadmill. The mice that exercised had an average of 1 110 primordial follicles, compared with 745 in the control group. These are the follicles that later begin growing and thereby deplete the reserve.
The authors focused on adiponectin, which is produced in the ovary partly by the granulosa cells surrounding the oocyte. Exercise increased adiponectin levels in the blood and ovaries, while reducing the activity of mTOR, a signaling system that initiates primordial follicle growth. In ovarian cultures, added adiponectin reduced the proportion of follicles that began growing. An mTOR activator partially reversed this effect.
In mice lacking adiponectin, the protective effect of exercise on the primordial follicle reserve was 56% smaller. When adiponectin production was suppressed only in the ovary, the effect was reduced by 76%. In these experiments, adiponectin was an important link between running and the slower recruitment of follicles from the reserve.
Seven-month-old female mice received AdipoRon, a compound that activates adiponectin receptors, for one month. After reaching 12 months of age, they produced more offspring than the control group. Most continued to produce offspring until 14–15 months of age.