Identification of Key Targets and Signaling Pathways of Vitamin D۳ in Recurrent Spontaneous Abortion Using Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulations

Recurrent spontaneous abortion (RSA) is a multifactorial reproductive disorder characterized by repeated pregnancy loss before fetal viability. Vitamin D۳ (VD۳) has been recognized as an important immunomodulator and endocrine regulator during pregnancy; however, its molecular mechanisms in RSA remain unclear. This study aimed to elucidate the potential targets and pathways of VD۳ in RSA using an integrative in silico approach. RSA-associated genes were obtained from DisGeNET, OMIM, and GeneCards, while VD۳-related targets were predicted using SwissTargetPrediction and the Similarity Ensemble Approach. Overlapping targets were used to construct a protein–protein interaction (PPI) network via STRING and Cytoscape, with hub genes identified using CytoHubba algorithms. Functional enrichment analysis was performed using GO and KEGG databases, followed by molecular docking (MOE) and molecular dynamics simulations (YASARA Dynamics). Network analysis identified CYP۱۹A۱, ESR۱, AR, and MDM۲ as key hub genes potentially mediating VD۳ effects in RSA. GO analysis revealed significant enrichment in biological processes related to cell proliferation, migration, and inflammatory response (FDR<۰.۰۵). KEGG pathway analysis highlighted the PI۳K–Akt, estrogen, steroid hormone biosynthesis, and p۵۳ signaling pathways. Molecular docking demonstrated favorable binding affinities between VD۳ and all hub targets, with the strongest interaction observed in CYP۱۹A۱. Molecular dynamics simulations further confirmed the structural stability of VD۳–protein complexes, with RMSD values remaining below ۳.۵ Å. In conclusion, VD۳ may be associated with RSA-related molecular networks through predicted multi-target interactions. Further experimental validation is required to confirm the functional relevance of the identified VD۳–target interactions in RSA.

کلیدواژه ها:

In Silico ، network pharmacology ، Recurrent spontaneous abortion ، Vitamin D۳