Zhou Xiao-Ling, Xu Jin-Jie, Ni Yan-Hong, Chen Xiao-Chun, Zhang Hong-Xia, Zhang Xing-Mei, Liu Wei-Juan, Luo Li-Li, Fu Yu-Cai
Department of Gynaecology and Obstetrics of the First Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong Province, 515041, People's Republic of China.
Laboratory of Cell Senescence, Shantou University Medical College, 22 Xin Ling Rd, Jinping District, Shantou, Guangdong Province, 515041, People's Republic of China.
J Ovarian Res. 2014 Oct 21;7:97. doi: 10.1186/s13048-014-0097-z.
The prevalence of obesity is increasing worldwide and significantly affects fertility and reproduction in both men and women. Our recent study has shown that excess body fat accelerates ovarian follicle development and follicle loss in rats. The aim of the present study is to explore the effect of SIRT1 activator SRT1720 on the reserve of ovarian follicle pool and ovarian lifespan of obese mice and the underlying mechanism associated with SIRT1 and mTOR signaling.
Adult female Kunming mice (n = 36) were randomly divided into three groups: the normal control (NC) group (n = 8), the caloric restriction (CR) group (fed 70% food of the NC group, n = 8) and the high-fat diet (HF) group (fed a rodent chow containing 20% fat, n = 20). After 4 months, the HF mice were further randomly divided into three groups: the control high-fat diet (CHF, n = 8) group (treated every day with an intraperitoneal injection of vehicle), the SRT1720 (SRT, n = 6) group (treated every other day with an intraperitoneal injection of SRT1720 (50 mg/kg)), the SRT1720 and nicotinamide (NAM, n = 6) group (treated every other day with an intraperitoneal injection of SRT1720 (50 mg/kg) and every day with an intraperitoneal injection of nicotinamide (100 mg/kg)). After 6 weeks of treatment, ovaries were harvested for histological and Western blotting analyses.
The body weight, ovary weight and visceral fat in the SRT group were significantly lower than those in the CHF group at the end of treatment. Histological analysis showed that the SRT mice had significantly greater number and percentage of primordial follicles, but lower number and percentage of corpora lutea and atretic follicles than the CHF mice and NAM mice. Western blot analysis demonstrated that the levels of SIRT1, SIRT6, FOXO3a and NRF-1 protein expression significantly increased in the ovaries of SRT mice, whereas those of mTORC1, p-mTOR, p-p70S6K, NFκB and p53 decreased compared to the CHF and NAM mice.
Our study suggests that SRT1720 may improve the follicle pool reserve in HF diet-induced obese female mice via activating SIRT1 signaling and suppressing mTOR signaling, thus extending the ovarian lifespan.
肥胖在全球范围内的患病率正在上升，并对男性和女性的生育能力和生殖产生重大影响。我们最近的研究表明，过多的体脂会加速大鼠卵巢卵泡的发育和卵泡丢失。本研究的目的是探讨SIRT1激活剂SRT1720对肥胖小鼠卵巢卵泡储备和卵巢寿命的影响以及与SIRT1和mTOR信号相关的潜在机制。
成年雌性昆明小鼠（n = 36）随机分为三组：正常对照组（NC组，n = 8）、热量限制组（CR组，给予NC组70%的食物，n = 8）和高脂饮食组（HF组，给予含20%脂肪的啮齿动物饲料，n = 20）。4个月后，将HF组小鼠进一步随机分为三组：对照高脂饮食组（CHF组，n = 8）（每天腹腔注射溶剂）；SRT1720组（SRT组，n = 6）（隔天腹腔注射SRT1720（50 mg/kg））；SRT1720与烟酰胺组（NAM组，n = 6）（隔天腹腔注射SRT1720（50 mg/kg），每天腹腔注射烟酰胺（100 mg/kg））。治疗6周后，收集卵巢进行组织学和蛋白质印迹分析。
治疗结束时，SRT组的体重、卵巢重量和内脏脂肪均显著低于CHF组。组织学分析显示，与CHF组和NAM组小鼠相比，SRT组小鼠的原始卵泡数量和百分比显著增加，而黄体和闭锁卵泡的数量和百分比则较低。蛋白质印迹分析表明，与CHF组和NAM组小鼠相比，SRT组小鼠卵巢中SIRT1、SIRT6、FOXO3a和NRF-1蛋白表达水平显著升高，而mTORC1、p-mTOR、p-p70S6K、NFκB和p53表达水平降低。
我们的研究表明，SRT1720可能通过激活SIRT1信号和抑制mTOR信号来改善高脂饮食诱导的肥胖雌性小鼠的卵泡储备，从而延长卵巢寿命。
