School of Basic Medical Sciences, Shandong University, Jinan 250012, China.
CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
Int J Mol Sci. 2021 Jun 18;22(12):6570. doi: 10.3390/ijms22126570.
A better understanding of the mechanism of primordial follicle activation will help us better understand the causes of premature ovarian insufficiency (POI), and will help us identify new drugs that can be applied to the clinical treatment of infertility. In this study, single oocytes were isolated from primordial and primary follicles, and were used for gene profiling with TaqMan array cards. Bioinformatics analysis was performed on the gene expression data, and Ingenuity Pathway Analysis was used to analyze and predict drugs that affect follicle activation. An ovarian in vitro culture system was used to verify the function of the drug candidates, and we found that curcumin maintains the ovarian reserve. Long-term treatment with 100 mg/kg curcumin improved the ovarian reserve indicators of AMH, FSH, and estradiol in aging mice. Mechanistic studies show that curcumin can affect the translocation of FOXO3, thereby inhibiting the PTEN-AKT-FOXO3a pathway and protecting primordial follicles from overactivation. These results suggest that curcumin is a potential drug for the treatment of POI patients and for fertility preservation.
更好地理解原始卵泡激活的机制将有助于我们更好地理解卵巢早衰（POI）的原因，并有助于我们识别可应用于不孕临床治疗的新药。在这项研究中，我们从原始卵泡和初级卵泡中分离出单个卵母细胞，并使用 TaqMan 阵列卡进行基因谱分析。对基因表达数据进行了生物信息学分析，并使用 Ingenuity 通路分析来分析和预测影响卵泡激活的药物。我们使用卵巢体外培养系统来验证候选药物的功能，发现姜黄素可维持卵巢储备。长期使用 100mg/kg 的姜黄素可改善衰老小鼠 AMH、FSH 和雌二醇等卵巢储备指标。机制研究表明，姜黄素可以影响 FOXO3 的易位，从而抑制 PTEN-AKT-FOXO3a 通路并保护原始卵泡免于过度激活。这些结果表明，姜黄素是治疗 POI 患者和生育力保存的潜在药物。
