Downregulation of FTO in the hippocampus is associated with mental disorders induced by fear stress during pregnancy

Mental disorders (MD), such as anxiety, depression, and cognitive impairment, are very common during pregnancy and predispose to adverse pregnancy outcomes; however, the underlying mechanisms are still under intense investigation. Although the most common RNA modification in epigenetics, N6-methyladenosine (m6A) has been widely studied, its role in MD has not been investigated. Here, we observed that fat mass and obesityassociated protein (FTO) are downregulated in the hippocampus of pregnant rats with MD induced by fear stress and demonstrated that FTO participates in and regulates MD induced by fear stress. In addition, we identified four genes with anomalous modifications and expression (double aberrant genes) that were directly regulated by FTO, namely Angpt2, Fgf10, Rpl21, and Adcy7. Furthermore, we found that these genes might induce MD by regulating the PI3K/Akt and Rap1 signaling pathways. It appears that FTO-mediated m6A modification is a key regulatory mechanism in MD caused by fear stress during pregnancy.

Automated summary

Mental disorders during pregnancy, such as anxiety and depression, can lead to adverse outcomes, but the underlying mechanisms are still being investigated. This study found that the FTO protein, which is involved in RNA modification, plays a role in and regulates mental disorders induced by fear stress in pregnant rats. The study also identified specific genes that are directly regulated by FTO and may be involved in the development of mental disorders.