Fear stress during pregnancy affects placental m6A-modifying enzyme expression and epigenetic modification levels

As the hub connecting mother and offspring, the placenta's normal development is vital for fetal growth. Fear stress can cause some structural alterations of the placenta and affect placental development and function.N6-methyladenosine (m6A) is the most abundant modification in mRNA, which can be involved in the regulation of placenta and embryo development. There are no reports regarding the potential role of the m6A modification in placental damage caused by fear stress during pregnancy. In this study, fear stress during pregnancy leads to the rise of methylated enzymes (METTL3, METTL14, WTAP), the decrease of the demethylase FTO, and the increase of the overall methylation level placenta of pregnant rats. MeRIP-seq data analysis showed 22,010 m6A peaks associated with 12,219 genes in the placenta of the model and 21,060 m6A peaks associated with 11,730 genes in the placenta of the control. The peaks were mainly concentrated in the coding region and the 3'UTR. In addition, 50 genes with abnormal modification and expression(double aberrant genes) were screened out by combining MeRIP-seq and RNA-seq data. Mefv, Erbb2, and Cgas were selected from 50 double aberrant genes, and MeRIP-qPCR and RT-qPCR were used to verify modification and expression levels. This suggests that m6A modifications may play an important role in fear stress induced placental dysfunction during pregnancy.