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ToolsYang, Yike, Jin, Huili, Qiu, Yuhan, Liu, Yamin, Wen, Li, Fu, Yong, Qi, Hongbo, Baker, Philip N. and Tong, Chao (2022) Reactive oxygen species are essential for placental angiogenesis during early gestation. Oxidative Medicine and Cellular Longevity, 2022. ISSN 1942-0900
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Abstract
Background. Preeclampsia (PE) is associated with insufficient placental perfusion attributed to maldevelopment of the placental vasculature. Reactive oxygen species (ROS) are implicated in angiogenesis, but their regulatory effects and mechanisms in placental vascular development remain unclear. Methods. Placental oxidative stress was determined throughout gestation by measuring 4-hydroxynonenal (4HNE) and malondialdehyde (MDA). The antioxidant MitoQ was administered to pregnant mice from GDs 7.5 to 11.5; placental morphology and angiogenesis pathways were examined on GDs 11.5 and 18.5. Moreover, we established a mouse mFlt-1-induced PE model and assessed blood pressure, urine protein levels, and placental vascular development on GDs 11.5 and 18.5. Human umbilical vein endothelial cells (HUVECs) were treated with various H2O2 concentrations to evaluate cell viability, intracellular ROS levels, and tube formation capability. MitoQ, an AKT inhibitor and an ERK1/2 inhibitor were applied to validate the ROS-mediated mechanism regulating placental angiogenesis. Results. First-trimester placentas presented significantly higher MDA and 4HNE levels. MitoQ significantly reduced the blood vessel density and angiogenesis pathway activity in the placenta on GDs 11.5 and 18.5. Serum sFlt-1 levels were elevated, and we observed poor placental angiogenesis and PE-like symptoms in cases with mFlt-1 overexpression. Moderate H2O2 treatment promoted HUVEC proliferation and angiogenesis, whereas these improvements were abolished by MitoQ, AKT inhibitor, or ERK1/2 inhibitor treatment. Conclusions. Moderate ROS levels are essential for placental angiogenesis; diminishing ROS with potent antioxidants during placentation decreases placental angiogenesis and increases PE risk. Therefore, antioxidant therapy should be considered carefully for normal pregnant women during early gestation.
| Item Type: | Article |
|---|---|
| Additional Information: | Data Availability: The datasets used or analyzed during the current study are available from the corresponding author upon reasonable request. Acknowledgments: This work was supported by grants from the National Natural Sciences Foundation of China (81871189, 82001580,U21A20346, and 82171662), the Chongqing Science and Technology Commission (cstc2019jcyj-msxmX0856 andcstc2021ycjh-bgzxm0192), and the Chongqing Health Committee (2019GDRC012 and 2020MSXM037) |
| Uncontrolled Keywords: | biochemistry,ageing,cell biology ,/dk/atira/pure/subjectarea/asjc/1300/1303 |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 08 May 2025 09:30 |
| Last Modified: | 08 May 2025 09:30 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/99213 |
| DOI: | 10.1155/2022/4290922 |
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