Li Wanjing, Xu Jinbang, Wang Jingyi, Zhang Junxin, Deng Disi
Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou 350001, P.R. China.
Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610075, P.R. China.
Comb Chem High Throughput Screen. 2024 Oct 14. doi: 10.2174/0113862073327087240926065629.
To study the mechanism by which curcumin regulates ovarian primordial follicle initiation in rats with triptolide-induced diminished ovarian reserve (DOR).
An in vitro gelatin sponge culture was performed on 3-day-old rat ovaries. After the establishment of the DOR model with triptolide, curcumin was administered for 3 days. Histological analysis and follicle counts were performed using H&E staining. ELISA detection of ovarian hormones in the culture medium (E2, FSH and LH), western blotting and Q-PCR for protein and mRNA expression (LTCONS-00011173, TGF-β1, Smad1, AMH, PTEN and GDF-9).
Ovarian primordial and growing follicles increased significantly after curcumin intervention (p < 0.05), FSH/LH and E2 levels were increased significantly (p < 0.05). Curcumin also significantly decreased the expression of LTCONS-00011173. Meanwhile, curcumin increased the expression of TGF-β, AMH, and GDF-9 (p < 0.05). In addition, curcumin increased Smad1 gene expression and protein phosphorylation in the ovary on the one hand (p < 0.05), but inhibited Smad1 and p-Smad1 protein expression on the other hand (p < 0.05). Moreover, curcumin decreased PTEN protein and mRNA expression (p < 0.05).
Curcumin activates primordial follicles in DOR model rats through TGF-β1 and downstream AMH signaling pathways and may limit follicle exhaustion through LncRNA.
研究姜黄素调节雷公藤甲素诱导的卵巢储备功能下降(DOR)大鼠卵巢原始卵泡启动的机制。
对3日龄大鼠卵巢进行体外明胶海绵培养。用雷公藤甲素建立DOR模型后,给予姜黄素3天。采用苏木精-伊红(H&E)染色进行组织学分析和卵泡计数。酶联免疫吸附测定(ELISA)检测培养基中的卵巢激素(雌二醇、促卵泡生成素和促黄体生成素),蛋白质免疫印迹法和实时荧光定量聚合酶链反应(Q-PCR)检测蛋白质和信使核糖核酸(mRNA)表达(LTCONS-00011173、转化生长因子-β1、Smad1、抗苗勒管激素、第10号染色体缺失的磷酸酶和张力蛋白同源物、生长分化因子-9)。
姜黄素干预后,卵巢原始卵泡和生长卵泡显著增加(p<0.05),促卵泡生成素/促黄体生成素和雌二醇水平显著升高(p<0.05)。姜黄素还显著降低了LTCONS-00011173的表达。同时,姜黄素增加了转化生长因子-β、抗苗勒管激素和生长分化因子-9的表达(p<0.05)。此外,姜黄素一方面增加了卵巢中Smad1基因表达和蛋白质磷酸化(p<0.05),但另一方面抑制了Smad1和磷酸化Smad1蛋白表达(p<0.05)。而且,姜黄素降低了第10号染色体缺失的磷酸酶和张力蛋白同源物蛋白和mRNA表达(p<0.05)。
姜黄素通过转化生长因子-β1和下游抗苗勒管激素信号通路激活DOR模型大鼠的原始卵泡,并可能通过长链非编码核糖核酸(LncRNA)限制卵泡耗竭。