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

Eur J Med Res. 2015 Mar 12;20(1):22. doi: 10.1186/s40001-015-0114-8.

Abstract

Background: Silent 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.

Methods: In 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.

Results: The 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.

Conclusions: Our 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caloric Restriction*
  • Female
  • Forkhead Box Protein O3
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Nuclear Respiratory Factor 1 / genetics
  • Nuclear Respiratory Factor 1 / metabolism
  • Ovarian Follicle / growth & development
  • Ovarian Follicle / metabolism*
  • Signal Transduction*
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism*
  • Sirtuins / genetics
  • Sirtuins / metabolism
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Forkhead Box Protein O3
  • Forkhead Transcription Factors
  • FoxO3 protein, mouse
  • Nrf1 protein, mouse
  • Nuclear Respiratory Factor 1
  • Tumor Suppressor Protein p53
  • Sirt6 protein, mouse
  • Sirt1 protein, mouse
  • Sirtuin 1
  • Sirtuins