Potential Role Of FoxO3a In The Regulation Of Trophoblast Development And Pregnancy Complications

The forkhead boxO3 a protein(FoxO3a)has been reported to regulate tumor invasion and migration,but little is known about the molecular mechanism or its role in trophoblast invasion and migration into the uterus.In this study,we aim to explore its role in trophoblast development and placenta-related pregnancy complications and the potential mechanism.Levels of FoxO3 a and its phosphorylated form(p-FoxO3a)in placental tissue from healthy pregnant women and preeclampsia patients were first compared.Then HTR-8/SVneo cells were transfected with lentiviral vectors to deplete and overexpress FoxO3 a.Western blot,immunohistochemistry,Cell Counting Kit-8,wound healing assay,Matrigel invasion assay,cell apoptosis,cell cycle assay,RNA sequencing,q RT-PCR and Ch IP-q PCR were performed on the cells to study the potential role of FoxO3 a and the underlying mechanism.We found the expression of FoxO3 a was decreased,while p-FoxO3 a was increased in preeclampsia placenta.FoxO3 a depletion significantly reduced transcription of the promoter region of intercellular cell adhesion molecule-1(ICAM1)gene in Ch IP assays,and led to reduced invasion and migration of trophoblast cells,arrested cell cycle in G1 phase and increased apoptosis under oxidative stress.Our results suggested that FoxO3 a may play a role in the regulation of trophoblast invasion and migration during placental development,which may be due to its affinity to the ICAM1 promotor.