Calorie restriction inhibits ovarian follicle development and follicle loss through activating SIRT1 signaling in mice

Abstract

BackgroundSilent information regulator 2 related enzyme 1 (SIRT1) is one of the key factors in the mechanism of calorie restriction (CR) extending lifespan of animals. The aim of the study is to investigate if CR prolongs ovarian lifespan in mice through activating SIRT1 signaling.MethodsIn the present study, 21 female C57BL/6 mice were divided into three groups: the control (n = 7), CR (n = 7), and SRT1720 (n = 7) groups. After the 26-week treatment, the number of ovarian follicles at each stage was counted, and Western blot was performed.ResultsThe number of surviving follicles in ovaries of the SRT1720 group was less than that of the CR group but more than that of the normal control (NC) group. The number of atretic follicles in the ovaries of the SRT1720 group was similar to that of the CR group but less than that of the NC group. The number of primordial follicles in the ovaries of the SRT1720 group was less than that of the CR group but more than that of the NC group. The numbers of primary follicles, secondary follicles, antral follicles, and corpora lutea in the SRT1720 group were similar to those in the CR group. Western blot analysis showed that the expression of SIRT1, SIRT6, FOXO3a, and NRF1 proteins was upregulated, and p53 was downregulated in both the CR group and the SRT1720 group compared to the control group.ConclusionsOur results indicate that CR inhibits the activation of primordial follicles and development of follicles at different stages, thus preserving the reserve of follicle pool (at least partly) through activating SIRT1 signaling.

Time‐restricted feeding improves the reproductive function of female mice via liver fibroblast growth factor 21

“…Various studies have focused on extending the reproductive span by chronic caloric restriction. 7,59,60 however, the reproductive capacity was shown to be impaired by a prolonged caloric restriction, resulting in subfertility or even infertility. 7,60 In the present study, TRF increased the number of offspring and successful pregnancies rate in mice fed both the chow diet and high-fat diet ( Figures 2D,G), which was coincident with the greater number of ovarian reservations found in the TRF groups ( Figure 1I).…”

Non-suckling starvation of neonatal mice promotes primordial follicle formation with activation of ovarian autophagy

“…Several studies have reported on the effects of starvation (or calorie restriction) on female reproductive function. The collective findings indicate that calorie restriction may inhibit the activation of PFs as well as follicular development and loss, thus extending ovarian lifespan by suppressing mTOR and activating SIRT1 signaling in adult rats [ 14 , 15 ].…”

The Role and Application of Sirtuins and mTOR Signaling in the Control of Ovarian Functions

“…These observations indicate that SIRT1, SIRT3, SIRT5, and SIRT6 can be markers of ovarian reserve and ovarian aging. Calorie restriction, which suppresses murine ovarian follicle development, was associated with a reduction in the follicular content of SIRT1 and SIRT6 [16]. Therefore, SIRTs 1, 3, 5, and 6 are potentially useful markers to characterize and to predict ovarian follicular development and related fecundity.…”

“…Unfortunately, the large-scale practical application of SIRTs in medicine, assisted reproduction, and animal biotechnology is limited by problems in their delivery or in the direct control of their expression via cDNA and small RNA constructs. The less time- and money-consuming approach is to promote SIRTs’ accumulation via caloric restriction [2,16] or mTOR regulators.…”

“…It can promote SIRT1 accumulation in various non-ovarian cells [5]. Caloric restriction induces the accumulation of SIRT1 in murine ovaries, which is associated with impairment of ovarian follicle development and follicle loss [16]. …”