Polycystic Ovary Syndrome and Ferroptosis: Following Ariadne's Thread

Background: Recent literature suggests that ferroptosis (FPT) may be a key player in polycystic ovary syndrome (PCOS) pathogenesis, but the underlying mechanism(s) remain(s) unclear. Aim: Therefore, herein, we made an effort to reproduce the molecular signature of the syndrome by including FPT and exploring novel drug targets for PCOS. Methods: (a) Our previously constructed PCOS interactions molecular network was extended with the addition of FPT-associated genes (interaction score above 0.7) and (b) gene set enrichment analysis was performed so as to detect over-represented KEGG pathways. Results: The updated interactome includes 140 molecules, 20 of which are predicted/novel, with an interaction score of 7.3, and 12 major hubs. Moreover, we identified 16 over-represented KEGG pathways, with FPT being the most overexpressed pathway. The FPT subnetwork is connected with the PCOS network through KDM1A. Conclusions: FPT cell death is involved in PCOS development, as its major hub TP53 was shown to be the most important hub in the whole PCOS interactome, hence representing a prioritized drug target.