Abstract
Purpose
To investigate the molecular mechanisms governing aquaporin-1 (AQP1)-mediated, mifepristone-induced angiogenesis and improve the understanding of low-dose mifepristone serving as an anti-implantation contraceptive drug.
Methods
Human umbilical vein endothelial cells (HUVECs) were used to explore the effects of different concentrations of mifepristone (0, 65, and 200 nmol/L) on the activity of angiogenesis. Forty-five pregnant mice during the “window of implantation” were treated with different concentrations of mifepristone. HUVECs’ proliferation was examined using a methyl thiazolyl tetrazolium (MTT) assay. The microvessel density (MVD) and the expression of AQP1 in endometrium were determined with immunohistochemical methods.
Results
The MVD and the expression of AQP1 were significantly higher than controls. Mifepristone at 200 nmol/L significantly affected HUVECs’ proliferation during culture over 12 h, and pretreatment with AQP1-specific siRNA significantly inhibited the mifepristone-enhanced cell proliferation.
Conclusions
Low-dose mifepristone increased angiogenesis in a manner involving AQP1. This affords a new insight into the molecular mechanism underpinning the angiogenic effects of low-dose mifepristone.
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Funding
This work was supported by the program for National Natural Science Foundation of China (No. 81701502).
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All authors made substantial contributions to conception and design, or acquisition of data, or analysis and interpretation of data; ZF and QZ involved in drafting the manuscript and revising it critically for important intellectual content; HL gave final approval to the version to be published. All authors read and approved the final manuscript.
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The procedures of this study were approved by the Animal Care and Use Committee of Zhejiang University (Hangzhou, China) and were in accordance with the university’s guidelines for animal research.
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Zhou, F., Qian, Z. & Huang, L. Low-dose mifepristone increased angiogenesis in a manner involving AQP1. Arch Gynecol Obstet 299, 579–584 (2019). https://doi.org/10.1007/s00404-018-4989-9
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DOI: https://doi.org/10.1007/s00404-018-4989-9