ti vation of primordial follicles. ii promoting the develop ment and maturity of ovarian follicles. iii promoting follicle apoptosis. These results were coincident with our previous findings. SIRT 1 signaling was involved in the regulation of ovarian follicle development Mammalian never SIRT1, the ortholog of yeast Sir2, is a class III histone deacetylase whose activation is dependent on nicotinamide adenine dinucleotide in the nucleus. It not only deacetylates histones, but also has a wide range of non histone sustrates, such as the forkhead bo class O family, p53 and nuclear factor ��B, etc. Accumulated evidence has revealed that SIRT1 is crucial for caloric restriction induced longev ity, and SIRT1 genetic variation is related to obesity, suggesting that SIRT1 is a key regulator of whole body energy balance.
SIRT1 also plays a role in repro ductive biology. SIRT 1 transgenic mice showed pheno types resembling CR and displayed prolonged lifespan, inhibited ovarian follicular development and delayed se ual maturity, whereas both male and female sirt1 null mice were barren. FO O3a is known as an important substrate of SIRT1. Mice with deletion of FO O3a gene have been shown to have abnormal ovar ian follicular development with early degeneration of oo cytes, resulting in age dependent infertility, whereas se ual maturity was delayed and follicle development was inhibited in oocyte specific FO O3a transgenic mice. Our previous study demonstrated that CR improved the follicle reserve and e tended ovarian lifespan with in creasing e pression of SIRT1 and SIRT6.
On the contrary, the level of SIRT1 and SIRT6 e pression in the ovaries decreased in obese rats. Kim et al. recently reported SIRT1 forms a comple with FO O3a and NRF1 on the SIRT6 promoter to positively regulated e pression of SIRT6. Our study also suggested that SIRT1 FO O3a NRF1 SIRT6 signaling may be involved in CR e tending ovarian lifespan mechanisms. Both SIRT 1 transgenosis and activators of SIRT 1 can mimic CR effect. However, it has remained elusive whether SIRT1 signaling plays a role in the development of ovarian follicles. Thus, we used SRT1720, the specific activator of SIRT1, to investigate its effect on the follicle development of the high fat diet induced obesity mice.
Our results showed that SRT1720 treatment caused an increase in the number and percentage of primordial follicles, which was comparable to CR treatment, suggest ing that SRT1720 may inhibit the activation of primordial follicles like CR. Although the numbers of secondary and antral Entinostat follicles were not significantly affected, the number www.selleckchem.com/products/chir-99021-ct99021-hcl.html and percentage of corpora lutea were decreased by the SRT1720 and CR treatment, suggesting that SRT1720 and CR may suppress follicle maturation. This may e plain that the SRT1720 treated and CR ovaries were smaller than those of the control. Moreover, both the number and percentage of atretic follicles were significantly decreased by SRT1720, suggesting that SRT1720 may inhibit follicu l