Aspirin Enhances the Protective Effect of Progesterone on Trophoblast Cell from Oxidative Stress and Apoptosis

• 作者: Shi Jia-Wei Yang Hui-Li Lai Zhen-Zhen Shen Hui-Hui Ruan Lu-Yu Wang Yan Qiu Xue-Min Xie Feng Li Ming-Qing
• 来源期刊: 生殖与发育医学（英文）
• 关键词: Apoptosis Aspirin Invasion Miscarriage Progesterone Progesterone Receptor Proliferation Reactive Oxygen Species Trophoblasts
• 年，卷（期）: 2021,（1）
• 所属期刊栏目: Original Article
• 页码范围: 1-8
• 页数: 8页
• 语种: 中文
• DOI: 10.4103/2096-2924.313686

摘要

Objective::Clinically, low-dose aspirin and progesterone are frequently used to prevent pregnancy loss. We investigated the effect of these drugs on the biological behavior of human extravillous trophoblasts in vitro. Methods::HTR-8/SVneo cells were cultured in vitro and treated with different concentrations of aspirin and progesterone. The proliferation, invasion, and apoptosis of HTR-8/SVneo cells were assessed using a cell counting Kit-8 assay, Matrigel Transwell assay, and Hoechst staining, respectively. Reverse transcriptase polymerase chain reaction was used to verify the expression of related genes. Reactive oxygen species (ROS) levels were detected using the 2,7-dichlorofluorescin diacetate assay. Results::Low-dose aspirin alone, progesterone alone, or aspirin plus progesterone upregulated the proliferation and invasion and decreased the apoptosis of HTR-8/SVneo cells. Moreover, the expression of marker of proliferation Ki-67 ( MKI67), matrix metalloproteinases 2 ( MMP2), and MMP9 was increased. In addition, low-dose aspirin plus progesterone exerted stronger anti-apoptosis effects than low-dose aspirin and progesterone alone. Interestingly, aspirin upregulated the expression of progesterone receptor ( PGR). Treatment with hydrogen peroxide (H 2O 2) promoted ROS production in HTR-8/SVneo cells; however, low-dose aspirin plus progesterone significantly restricted H 2O 2-mediated ROS production and apoptosis in HTR-8/SVneo cells. Conclusions::These data suggest that low-dose aspirin and progesterone promote proliferation and invasion and cooperatively reduce oxidative stress and apoptosis in trophoblasts in vitro. These results may provide an experimental basis for the combined application of aspirin and progesterone to prevent unexplained recurrent spontaneous miscarriage, especially in patients with trophoblast dysfunction.