Open AccessPotential role of FoxO3a in the regulation of trophoblast development and pregnancy complications
Author(s) -
Chen Hao,
Tang Xin,
Han TingLi,
Zhu JiaNan,
Zhou Wei,
Baker Philip N.,
Chen Chang,
Zhang Hua
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16499
Subject(s) - trophoblast , microbiology and biotechnology , biology , cell migration , apoptosis , cell cycle , transfection , western blot , matrigel , cell growth , andrology , cell , placenta , cell culture , medicine , gene , pregnancy , genetics , fetus
Abstract The forkhead box O3a protein (FoxO3a) has been reported to regulate tumour 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 FoxO3a and its phosphorylated form (p‐FoxO3a) in placental tissue from healthy pregnant women and pre‐eclampsia patients were first compared. Then, HTR‐8/SVneo cells were transfected with lentiviral vectors to deplete and overexpress FoxO3a. Western blot, immunohistochemistry, Cell Counting Kit‐8, wound‐healing assay, Matrigel invasion assay, cell apoptosis, cell cycle assay, RNA sequencing, qRT‐PCR and ChIP‐qPCR were performed on the cells to study the potential role of FoxO3a and the underlying mechanism. We found the expression of FoxO3a was decreased, whereas p‐FoxO3a was increased in pre‐eclampsia placentae. FoxO3a depletion significantly reduced transcription of the promoter region of intercellular cell adhesion molecule‐1 (ICAM1) gene in ChIP 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 FoxO3a may play a role in the regulation of trophoblast invasion and migration during placental development, which may be because of its affinity to the ICAM1 promotor.