Problem: Unexplained recurrent spontaneous abortion (URSA) is one of the most frustrating and confounding conditions in reproductive medicine, and its exact pathogenesis has not been clearly established.
Method of study: In this study, we used RNA sequencing to characterize the mRNA and lncRNA expression profiles in peripheral blood. Thereafter, enrichment analysis was performed to determine the functions of the differentially expressed genes, and Cytoscape was used to construct lncRNA-mRNA interaction networks.
Results: Our results showed that the peripheral blood of patients with URSA has distinct mRNA and lncRNA expression profiles, with a total of 359 mRNAs and 683 lncRNAs being differentially expressed. Moreover, the top hub genes, including IGF1, PPARG, CCL3, RETN, SERPINE1, HESX1, and PRL, were identified and further validated using real-time quantitative PCR. Furthermore, we demonstrated a lncRNA-mRNA interaction network that achieved 12 key lncRNAs and their targeted mRNAs are involved in systemic lupus erythematosus, allograft rejection, and complement and coagulation cascades. Finally, the correlation between immune cell subtypes and IGF1 expression was evaluated; a negative correlation was observed with the proportion of natural killer cells, which increased significantly in URSA.
Conclusion: We identified seven top hub genes, constructed a lncRNA-related network and suggested that IGF1 plays a key role in regulating maternal immune response by affecting NK and T cells' function, which helps to identify the pathogenesis of URSA.
Keywords: RNA sequencing; lncRNA; lncRNA-mRNA interaction network; protein-protein interaction; unexplained recurrent spontaneous abortion.
© 2023 The Authors. American Journal of Reproductive Immunology published by John Wiley & Sons Ltd.