Li Xinshu, Chen Xue, Guo Hua
Ningxia Medical University, Yinchuan, 750004, Ningxia, China.
Department of Gynecology, General Hospital of Ningxia Medical University, Yinchuan, 750004, Ningxia, China.
BMC Womens Health. 2025 Apr 29;25(1):210. doi: 10.1186/s12905-025-03710-6.
Diminished ovarian reserve (DOR) is a common female reproductive aging disease, which showed significant impacts on the quality of life and fertility in women. Plasminogen activator inhibitor 1 (PAI-1) is considered to be a major profibrotic factor. The development of DOR is closely related to ovarian fibrosis. The aim of the study was to investigate the expression of PAI-1,which is clinically relevant to DOR.
This case-control study included 40 infertile women with DOR and 40 infertile women with normal ovarian function. PAI-1 and reproductive hormones in serum and follicle fluid were determined in all subjects. Receiver operating characteristic curve (ROC) was applied to evaluate PAI-1 in prediction and diagnosis of DOR. The mRNA and protein expression of PAI-1 in KGN cells induced by cyclophosphamide (CTX) were observed by Western blot (WB) and quantitative real-time PCR (qRT-PCR).
The sensitivity and specificity of PAI-1 levels in serum/follicular fluid for predicting DOR were 90%/97.5% and 70%/82.5%, respectively. The AUC of PAI-1 in follicular fluid was 0.955(95% CI 0.913-0.997), which cutoff level and Youden index were 68.58 ng/mL and 0.825 for DOR. PAI-1 in serum and follicle fluid showed negative association with Anti-Müllerian hormone (AMH) and antral follicle count (AFC) (serum r= -0.391,r= -0.453;follicle fluid r= -0.486,r= -0.534;p < 0.01), however, they were positively correlated with follicle-stimulating hormone (FSH) and follicle-stimulating hormone/luteinizing hormone (FSH/LH) (serum r = 0.307,r = 0.388;follicle fluid r = 0.300,r = 0.384;p < 0.05). The ROC analysis indicated that serum PAI-1 has great prediction of DOR, with an AUC of 0.841, a sensitivity of 90%, and a specificity of 70%. Additionally, the qRT-PCR results demonstrated that the mRNA levels of PAI-1 increased in the CTX-induced cells (P < 0.05). The western blot results were consistent with qRT-PCR results.
Our study reveals that the expression of PAI-1 is higher in serum and follicular fluid of DOR patients. And it is positively correlated with FSH, FSH/LH and negatively correlated with AMH/AFC, which is necessary to investigate the role of PAI-1 in regulating the growth and development of follicles and the pathogenesis of DOR in future.
卵巢储备功能减退（DOR）是一种常见的女性生殖衰老疾病，对女性的生活质量和生育能力有显著影响。纤溶酶原激活物抑制剂1（PAI-1）被认为是一种主要的促纤维化因子。DOR的发展与卵巢纤维化密切相关。本研究的目的是探讨PAI-1的表达，其在临床上与DOR相关。
本病例对照研究包括40例DOR不孕妇女和40例卵巢功能正常的不孕妇女。测定所有受试者血清和卵泡液中的PAI-1及生殖激素。应用受试者工作特征曲线（ROC）评估PAI-1在DOR预测和诊断中的作用。通过蛋白质印迹法（WB）和定量实时聚合酶链反应（qRT-PCR）观察环磷酰胺（CTX）诱导的KGN细胞中PAI-1的mRNA和蛋白表达。
血清/卵泡液中PAI-1水平预测DOR的敏感性和特异性分别为90%/97.5%和70%/82.5%。卵泡液中PAI-1的AUC为0.955（95%CI 0.913-0.997），DOR的临界值和尤登指数分别为68.58 ng/mL和0.825。血清和卵泡液中的PAI-1与抗苗勒管激素（AMH）和窦卵泡计数（AFC）呈负相关（血清r = -0.391，r = -0.453；卵泡液r = -0.486，r = -0.534；p < 0.01），然而，它们与促卵泡激素（FSH）和促卵泡激素/黄体生成素（FSH/LH）呈正相关（血清r = 0.307，r = 0.388；卵泡液r = 0.300，r = 0.384；p < 0.05）。ROC分析表明血清PAI-1对DOR有很好的预测价值，AUC为0.841，敏感性为90%，特异性为70%。此外，qRT-PCR结果表明CTX诱导的细胞中PAI-1的mRNA水平升高（P < 0.05）。蛋白质印迹结果与qRT-PCR结果一致。
我们的研究表明，DOR患者血清和卵泡液中PAI-1的表达较高。它与FSH、FSH/LH呈正相关，与AMH/AFC呈负相关，未来有必要研究PAI-1在调节卵泡生长发育及DOR发病机制中的作用。
