a1-antitrypsin, a new biomarker of polycystic ovary syndrome by changing its expression and rhythm.

BACKGROUND: Previous proteomic studies have demonstrated the potential for identifying specific diagnostic biomarkers in the plasma and follicular fluid of patients with polycystic ovary syndrome (PCOS), which was utilized to elucidate the underlying etiology of PCOS. Our study aimed to identify differences in serum protein expression between newly diagnosed PCOS patients and healthy controls and to identify novel biomarkers for the diagnosis and treatment of women with PCOS. We focused on the association between a1-antitrypsin (A1AT) levels and hormonal-metabolic parameters in women with PCOS. MATERIALS AND METHODS: This study involved 70 newly diagnosed PCOS patients and 78 healthy controls. We measured serum A1AT levels via Label-free quantitative proteomics and ELISA methods. Additionally, blood samples from 10 PCOS patients and 10 healthy controls were collected over 24 h. Furthermore, we established a mouse model of PCOS to detect serum A1AT levels and the A1AT mRNA expressions of liver tissues. We also analyzed the mRNA expressions of several clock-related genes in the hypothalamus, pituitary, ovary and liver tissues. RESULTS: Serum A1AT levels were higher in women with newly diagnosed PCOS than controls. Meanwhile, the levels of serum IL-6 and TNF-a in PCOS patients were higher than those of healthy controls. A1AT levels showed a positive correlation with luteinizing hormone (LH) and testosterone levels, whereas it showed a negative correlation with sex hormone-binding protein in women with PCOS. However, some metabolic markers were not significantly associated with the level of A1AT. Interestingly, serum A1AT level exhibited a significant diurnal rhythm in the control group expectedly, while it was not diurnal in the PCOS group. Animal studies suggest that the increase in A1AT levels observed in PCOS could be associated with alterations in the expression of clock-related genes in reproductive tissues. CONCLUSIONS: Increased A1AT levels in women with newly diagnosed PCOS were related to androgens, suggesting that A1AT might be a potential biomarker for PCOS. Serum A1AT levels exhibited a significant diurnal rhythm in the control group, while it was not diurnal in the PCOS group. These findings provide a theoretical foundation for understanding the role of the circadian clock in the prevention and treatment of PCOS in females with biorhythm disorders.