Plasminogen activator inhibitor 1 is a novel predictor in human serum/follicular fluid for diminished ovarian reserve

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.