Altered hemostatic dynamics and its regulation in follicular microenvironment of women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS), presents with gynecological and metabolic issues such as anovulatory infertility, insulin resistance, hyperandrogenism, and obesity, and long-term cardiometabolic risks. Emerging evidence highlights coagulation-fibrinolysis balance influences essential ovarian functions, including ovulation, corpus luteum function, granulosa cell luteinization, and ECM remodeling. This study explores the relatively understudied coagulation and fibrinolytic factors in the ovarian microenvironment in Indian women. This case-control study examined the hemostatic potential of the follicular microenvironment in PCOS (n = 35) and controls (n = 30) by analyzing coagulation and fibrinolytic profiles in follicular fluid (FF), and granulosa cells (GCs). We observed significantly reduced transcript expressions of fibrinolytic factors including serine proteinase inhibitor (SERPINE1), tissue-type plasminogen activator (PLAT), coagulation factor fibrinogen gamma (FGG) in PCOS GCs. Conversely, transcript levels of thrombomodulin (THBD) and urokinase plasminogen activator receptor (PLAUR) were significantly higher in GCs of PCOS women compared to controls. Levels of both plasminogen activators, PLAT and PLAU, along with anticoagulant proteins, tissue factor pathway inhibitor and protein S were markedly declined, while plasminogen, THBD and histidine rich glycoprotein levels were significantly raised in FF of women with PCOS. Further, the construction of miRNA-mRNA regulatory network suggested that miRNAs may also be involved in hemostatic regulation in follicle microenvironment of PCOS. Our study showed that altered profiles of coagulation and fibrinolysis factors within follicular microenvironment of PCOS could contribute to disrupted hemostatic balance, mainly evidenced by compromised fibrinolysis. This may have significant implications for ovulatory dysfunction due to altered rupture, ECM remodeling and cumulus expansion in affected women.