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Unveiling the role of miRNAs in Diminished Ovarian Reserve: an in silico network approach

C. Cimini,A. Taraschi,M. Ramal-Sanchez,Alessia Colosimo,Carlo Di Carlo,R. Belda-Pérez,Luca Valbonetti,G. Capacchietti,N. Bernabò,B. Barboni

Published 2025 in Systems Biology in Reproductive Medicine

ABSTRACT

Abstract MicroRNAs (miRNAs) have acquired an increased recognition to unravel the complex molecular mechanisms underlying Diminished Ovarian Reserve (DOR), one of the main responsible for infertility. To investigate the impact of miRNA profiles in granulosa cells and follicular fluid, crucial players in follicle development, this study employed a computational network theory approach to reconstruct potential pathways regulated by miRNAs in granulosa cells and follicular fluid of women suffering from DOR. Available data from published research were collected to create the FGC_MiRNome_MC, a representation of miRNA target genes and their interactions. 365 hubs were identified within the network, representing potential key regulators, and 210 nodes that act as both hubs and bottlenecks (H&BN nodes), suggesting that they may control the information flow within the network. GO enrichment analysis of the 210 H&BN nodes revealed their involvement in fundamental cellular processes relevant to ovarian function. In particular, the cluster analysis identified several shared pathways between cluster 1 and cluster 2 involved in the RAS/MAPK pathway, which plays a critical role in cell proliferation, differentiation and survival. These findings suggest that miRNAs play a significant role in DOR and highlight the potential of the RAS/MAPK pathway as a target for further investigation. Additionally, the genes identified as both hubs and bottlenecks revealed interesting connections to reproductive health in KO mice models. This in silico approach provides valuable insights into potential biomarkers and therapeutic targets for age-related reproductive disorders.

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