Ezrin, radixin, and moesin are novel citrullinated proteins in the decidua during pregnancy

For a successful pregnancy, decidualization is a crucial process involving the significant transformation of endometrial stromal cells surrounding the implanting blastocysts. Disruption of this process can lead to the breakdown of the fetomaternal interface and result in early pregnancy loss. However, the precise mechanisms governing this process remain incompletely understood. This study aimed to elucidate the impact of citrullination, a post-translational modification, on decidualization in mice and humans. Immunohistochemical analysis and immunoprecipitation followed by immunoblotting were performed on mouse and human uterine tissues. In this study, we showed that ezrin/radixin/moesin (ERM) proteins are expressed in decidual and endothelial cells within the decidua during pregnancy, with their expression patterns significantly influenced by two factors: citrullination mediated by peptidylarginine deiminase enzymes and sphingosine kinase activity. Notably, ERM proteins were found to undergo citrullination exclusively in the decidua during pregnancy, but not in interimplantation tissues during pregnancy or in nonpregnant uteri in mice. Similar findings were observed in human decidual tissues from cases of spontaneous abortion and elective termination. In conclusion, this study demonstrates that ERM proteins undergo citrullination in the decidua during early pregnancy in both mice and humans. Our findings provide important insights into the molecular changes involved in pregnancy, particularly decidualization.