Link between iron-mediated lipid peroxidation and polycystic ovary syndrome (PCOS): exploring the genes underlying iron regulatory mechanism.

Objective: Mechanism underlying the etiology of polycystic ovary syndrome (PCOS) is still debatable. Present study explores the link between iron-mediated ferroptosis and PCOS.

Methodology: Blood samples were collected from 150 PCOS females along with healthy controls. Expression analysis of FTH1, NCOA4, GPX4, HAMP, A2M and HP genes was estimated by RT-qPCR. Serum was used for estimation of lipid peroxidation, peroxidase enzyme, ferritin and total protein.

Results: Relative expression of FTH1 (P < 0.05), HAMP (P < 0.01), GPX4, A2M, HP (P < 0.001) was downregulated and NCOA4 (P < 0.001) was upregulated in PCOS group compared to control. A significant difference was observed in mRNA expression of selected genes when ≤ 30year age group PCOS was compared to > 30year age PCOS group and their respective controls. Deregulation of gene expression was prominent in PCOS group with obese and overweight BMI compared to underweight and normal BMI group. Menstrual cycle length and marital status of PCOS females had no significant association with selected gene expression. Expression deregulation in targeted genes was observed in PCOS patients with complaints of either diabetes, high blood pressure or both. Increased level of lipid peroxidation, serum ferritin and total protein, while decreased peroxidase activity was observed in PCOS group (P < 0.001) compared to control.

Conclusion: The present study postulated the role of iron overload in trigger of ferroptosis following elevated lipid peroxidation and low peroxidase activity. Moreover, unveil the association of genes related to iron-regulating metabolism with etiology of underlying PCOS mechanism.