Intrauterine growth retardation-associated syncytin b hypermethylation in maternal rat blood revealed by DNA methylation array analysis

Abstract

Background: Emerging evidence suggests that DNA methylation in maternal blood is a promising target for intrauterine growth retardation (IUGR) screening, a common developmental toxicity. Here, we aimed to screen out IUGR-related DNA methylation status in maternal blood via high-throughput profiling. Methods: Pregnant Wistar rats were subcutaneously administered nicotine (1 mg/kg) twice per day from gestational day (GD) 11 to GD20 to establish the IUGR model. MeDIP array assays and the following GO analysis were used to evaluate DNA methylation status in maternal blood. One placental development-associated gene was selected for further confirmation. Results: Genes regulating the development of multiple organs and major body systems had changed DNA methylation frequencies in the maternal blood of IUGR rats. Placental development, which can affect the development of multiple fetal organs and induce IUGR, is a hypermethylated cluster consisting of four significantly changed genes, including syncytin b (Synb), Lrrc15, Met, and Tex19.1. With the most significant change, Synb hypermethylation in maternal blood was confirmed by bisulfite-sequencing PCR (BSP). Moreover, decreased Synb expression and histological changes were observed in IUGR placentae. Conclusion: The IUGR-associated DNA methylation profile in maternal blood, such as placenta-related Synb hypermethylation, provides evidence for further studies on possible IUGR biomarkers.