HIF‑1α affects trophoblastic apoptosis involved in the onset of preeclampsia by regulating FOXO3a under hypoxic conditions

Zhang,Zhan; Huang,Chenxi; Wang,Ping; Gao,Junjun; Liu,Xin; Li,Yingying; Yan,Shujun; Shi,Ying

doi:10.3892/mmr.2020.11050

HIF‑1α affects trophoblastic apoptosis involved in the onset of preeclampsia by regulating FOXO3a under hypoxic conditions

Authors:
- Zhan Zhang
- Chenxi Huang
- Ping Wang
- Junjun Gao
- Xin Liu
- Yingying Li
- Shujun Yan
- Ying Shi
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Affiliations: Department of Clinical Laboratory, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
Published online on: April 1, 2020 https://doi.org/10.3892/mmr.2020.11050
Pages: 2484-2492
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Preeclampsia (PE) is a pregnancy-specific syndrome that has severe implications on perinatal mortality and morbidity. Excessive apoptosis of trophoblasts induced by hypoxia may be associated with the development of PE, but the exact pathogenesis is unknown. Forkhead box O transcription factor 3a (FOXO3a) is activated under hypoxic conditions. Furthermore, hypoxia‑inducible factor‑1α (HIF‑1α) is sensitive to variations in partial oxygen pressure. Thus, the aims of the present study were to investigate the expression levels of HIF‑1α and FOXO3a in placental samples of early onset severe PE, and their effect on trophoblastic apoptosis under hypoxic conditions. Cobalt chloride was used to establish the hypoxic model. The present study examined the expression levels of HIF‑1α and FOXO3a in the placental tissues and HTR8/SVneo cells under hypoxic conditions. It was found that HIF‑1α and FOXO3a were highly expressed in placental tissues of patients with PE and in HTR8/SVneo cells under hypoxic conditions. Furthermore, knockdown of FOXO3a using a specific small interfering RNA (siRNA) decreased apoptosis in HTR8/SVneo cells. Moreover, it was found that after knockdown of HIF‑1α using siRNA, FOXO3a expression and the apoptotic rate were reduced in HTR8/SVneo cells. Therefore, the present results indicated that the elevated expression of HIF‑1α increased trophoblastic apoptosis by regulating FOXO3a, which may be involved in the pathogenesis of PE.

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