Objective To investigate the mechanism of unexplained recurrent spontaneous abortion induced by m6A modification disorder of early growth response 1 (EGR1). Methods Thirty patients with unexplained recurrent spontaneous abortion (the observation group) and 30 women with normal early pregnancy undergoing termination (the control group) were enrolled as the research subjects. The mRNA sequence of EGR1 was obtained from the NCBI database and input into the SRAMP database to predict m6A modification sites of EGR1. The real⁃time fluorescent quantitative PCR was used to detect the mRNA expressions of EGR1, erythropoietin⁃producing hepatocellular receptor B4 (EPHB4), and vascular endothelial growth factor (VEGF) in chorionic tissues of both groups. The methylated RNA immunoprecipitation quantitative PCR was performed to assess m6A modification enrichment of EGR1 in chorionic tissues of the two groups. The Western blot was adopted to determine protein expressions of EGR1, EPHB4, and VEGF in chorionic tissues of the two groups. Immunohistochemical staining was conducted to quantify microvessel density (MVD) in chorionic tissues of the two groups. Results Multiple potential m6A modification sites were predicted in EGR1. The observation group exhibited higher mRNA and protein expressions of EGR1 but lower mRNA and protein expressions of EPHB4 and VEGF compared to the control group (P<0.05). The m6A modification enrichment of EGR1 was reduced in the observation group than in the control group (P<0.05). Additionally, MVD was lower in the observation group than in the control group (P<0.05). Conclusion Level of m6A modification of EGR1 in chorionic tissues of patients with unexplained recurrent spontaneous abortion decreases, and m6A modification disorder of EGR1 may up⁃regulate EGR1 expression while down⁃regulating EPHB4 and VEGF expressions, thereby inhibiting the formation of MVD in chorionic tissues and contributing to unexplained recurrent spontaneous abortion pathogenesis.  

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