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Downregulation of HIF-2α Enhances Apoptosis and Limits Invasion in Human Placental JEG-3 Trophoblast Cells

  • Genetics: Original Article
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Abstract

Pre-eclampsia, one of the major disorders of pregnancy, is characterized by inadequate trophoblast invasion and defective trophoblast-mediated remodeling of placental vasculature. Hypoxia-inducible transcription factor (HIF)-2α plays a critical role in regulating cellular function of trophoblasts; however, its role in placental development and in the pathogenesis of pre-eclampsia remains elusive. CCK-8 assay was used to detect cell viability. Invasion assay was performed to determine the effect of HIF-2α on trophoblast function. Flow cytometry was used for detecting apoptosis and cell cycle. The mRNA and protein expressions of HIF-2α, VEGF, iNOS, and ET-1 were determined by quantitative real-time PCR and western blot techniques. The roles of HIF-2α in JEG-3 trophoblast cells were examined using siRNA technology. The presence of HIF-2α siRNA reduced the levels of cell viability after 48 h incubation, and the cell viability further reduced at 72 h. Besides, HIF-2α siRNA enhanced trophoblast apoptosis, as determined by flow cytometric measurement. Increased G1-phase and decreased S-phase cell population were induced by HIF-2α siRNA based on the determination of cell cycle distribution using propidium iodide staining. Furthermore, the invasive ability of JEG-3 trophoblasts was significantly reduced by HIF-2α siRNA. In addition, knockdown of the HIF-2α gene significantly decreased VEGF, iNOS, and ET-1 levels in JEG-3 human trophoblasts. Our findings provide preliminary evidence of the functions of HIF-2α in trophoblast biology and suggest that the downregulation of HIF-2α enhances cell apoptosis and limits trophoblast invasion.

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Data Availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Code Availability

Not applicable.

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Funding

This study was supported by National Natural Science Foundation of China (grant number 81760276)

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Authors and Affiliations

  1. Department of Obstetrics, Qinghai University Affiliated Hospital, No. 29, Tongren Road, Chengxi District, Xining, 810000, China

    Yingying Xie, Meng Ma, Mengting Xu, Qin Li, Zhuojia Yang & Cenying He

  2. Breast and Thyroid Surgery, Qinghai University Affiliated Hospital, Xining, China

    Haining Zhao

  3. Department of Nephrology, Qinghai University Affiliated Hospital, Xining, China

    Pengli Luo

Authors
  1. Yingying Xie
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  2. Haining Zhao
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  3. Pengli Luo
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  4. Meng Ma
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  5. Mengting Xu
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  6. Qin Li
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  7. Zhuojia Yang
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  8. Cenying He
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Contributions

Yingying Xie contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Pengli Luo, Haining Zhao, Meng Ma, Mengting Xu, and Qin Li. The first draft of the manuscript was written by Zhuojia Yang and Cenying He, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Yingying Xie.

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This study contains no human participants or tissues. Ethical approval and informed consent are not applicable for this study.

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Xie, Y., Zhao, H., Luo, P. et al. Downregulation of HIF-2α Enhances Apoptosis and Limits Invasion in Human Placental JEG-3 Trophoblast Cells. Reprod. Sci. 28, 2710–2717 (2021). https://doi.org/10.1007/s43032-021-00581-8

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  • DOI: https://doi.org/10.1007/s43032-021-00581-8

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