Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China.
Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200090, China.
Aging (Albany NY). 2022 Mar 11;14(5):2335-2347. doi: 10.18632/aging.203942.
To establish an oxidative stress-induced model of premature ovarian insufficiency (POI) and to explore the effect of SIRT1 and mitochondrial oxidative phosphorylation on the ovarian reserve.
Mice were treated with intraperitoneal injections of 3-nitropropionic acid (3-NPA) at different doses and for different time periods to induce a model of POI. Subsequently, the efficiency of each regimen was evaluated. The expression of SIRT1 in ovarian tissue was examined. Then, SIRT1 was knocked down in human luteinized granulosa cells (GCs), and its function and related receptor and gene expression were examined. Finally, a SIRT1 antagonist and agonist were used to explore the effects of SIRT1 on ovarian function and on the change in mitochondrial oxidative phosphorylation complexes (OXPHOS).
Decreases in ovarian reserve were successfully induced through the intraperitoneal injection of 40 mg/kg 3-NPA for 3 weeks, and SIRT1 was down-regulated in the model group. The knockdown of SIRT1 impaired the estrogen synthesis capacity of human GCs and decreased the expression of related genes. 3-NPA and SIRT1 antagonist Ex-527 decreased ovarian function and inhibited OXPHOS. In contrast, the SIRT1 agonist resveratrol promoted the recovery of ovarian function in the model group and improved OXPHOS. Additionally, P53, CASPASE 3, and BAX were down-regulated and BCL2 was up-regulated in the 3-NPA and Ex-527 groups; opposite trends were observed after resveratrol treatment.
The intraperitoneal injection of 40 mg/kg 3-NPA for 3 weeks could effectively induce POI. The increase in oxidative stress inhibited SRIT1 and mitochondrial oxidative phosphorylation, inducing follicular apoptosis.
建立氧化应激诱导的早发性卵巢功能不全（POI）模型，探讨 SIRT1 和线粒体氧化磷酸化对卵巢储备的影响。
采用不同剂量和不同时间腹腔注射 3-硝基丙酸（3-NPA）诱导 POI 模型，评价各方案的效果。检测卵巢组织中 SIRT1 的表达。然后，在人黄素化颗粒细胞（GCs）中敲低 SIRT1，检测其功能及相关受体和基因表达。最后，使用 SIRT1 拮抗剂和激动剂探讨 SIRT1 对卵巢功能及线粒体氧化磷酸化复合物（OXPHOS）变化的影响。
腹腔注射 40mg/kg 3-NPA 3 周可成功诱导卵巢储备下降，模型组 SIRT1 下调。SIRT1 敲低后，人 GCs 雌激素合成能力受损，相关基因表达减少。3-NPA 和 SIRT1 拮抗剂 Ex-527 降低卵巢功能，抑制 OXPHOS。相反，SIRT1 激动剂白藜芦醇促进模型组卵巢功能恢复，改善 OXPHOS。此外，3-NPA 和 Ex-527 组中 P53、CASPASE 3 和 BAX 下调，BCL2 上调；而白藜芦醇处理后则出现相反的趋势。
腹腔注射 40mg/kg 3-NPA 3 周可有效诱导 POI。氧化应激增加抑制 SIRT1 和线粒体氧化磷酸化，诱导卵泡凋亡。
