Potential role of FoxO3a in the regulation of trophoblast development and pregnancy complications

Chen, Hao, Tang, Xin, Han, Ting-Li, Zhu, Jia-Nan, Zhou, Wei, Baker, Philip N., Chen, Chang and Zhang, Hua (2021) Potential role of FoxO3a in the regulation of trophoblast development and pregnancy complications. Journal of Cellular and Molecular Medicine, 25 (9). pp. 4363-4372. ISSN 1582-1838

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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.

Item Type:	Article
Additional Information:	DATA AVAILABILITY STATEMENT: The data that support the findings of this study are available from the corresponding author upon reasonable request. Funding: National Natural Science Foundation of China. Grant Numbers: 81971406, 81771607, 81871185, 81961128004, 81701477, 82071671; National Key Research and Development Program of Reproductive Health & Major Birth Defects Control and Prevention. Grant Number: 2016YFC1000407; Chongqing Health Commission. Grant Numbers: 2017ZDXM008, 2018ZDXM024; Chongqing Science & Technology Commission. Grant Numbers: stc2017jcyjBX0060, cstc2018jcyjAX0359
Uncontrolled Keywords:	forkhead box o3a protein,intercellular cell adhesion molecule-1,migration,pre-eclampsia,transcriptomics
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Depositing User:	LivePure Connector
Date Deposited:	30 May 2025 13:30
Last Modified:	04 Jun 2025 08:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/99351
DOI:	10.1111/jcmm.16499

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