Heparin prevents oxidative stress-induced apoptosis in human decidualized endometrial stromal cells
Heparin prevents oxidative stress-induced apoptosis in human decidualized endometrial stromal cells
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DOI：
10.1007/s00795-019-00220-x
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发表时间：
2019-03
影响因子：
1.8
通讯作者：
S. Tamaru;T. Kajihara;Yumi Mizuno;Natsuko Takano;H. Tochigi;Tomomi Sato;O. Ishihara
中科院分区：
文献类型：
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作者：
S. Tamaru;T. Kajihara;Yumi Mizuno;Natsuko Takano;H. Tochigi;Tomomi Sato;O. Ishihara
临床试验表明，在黄体期给予肝素对植入和活产率有有益的影响。肝素对人子宫内膜间质细胞（HESCs）有直接作用，不依赖于其抗凝作用。然而，肝素在去个体化过程中的准确作用仍不清楚。在这里，我们证明HESCs在脱个体化后对氧化应激具有显著的抵抗性，并且我们假设肝素可能直接作用于HESCs的脱个体化，从而改善植入。为了验证这一假设，我们建立了HESC原代培养并进行了繁殖，然后用8-溴- camp、醋酸甲孕酮、加或不加肝素进行了分离培养。我们用过氧化氢（H2O2）作为活性氧（ROS）的来源处理细胞。在去个体化HESCs中加入肝素可诱导泌乳素分泌。肝素处理的去个别化HESCs可防止氧化应激诱导的细胞凋亡。肝素诱导叉头转录因子FOXO1的核积累及其下游靶标ROS清除剂超氧化物歧化酶2的表达。这些结果表明，肝素处理的去个别化HESCs获得了进一步的抗氧化应激能力，表明肝素可能改善了植入环境。
Clinical trials have shown that administering heparin during the luteal phase has beneficial effects on implantation and live birth rates. Heparin exerts direct effects on decidual human endometrial stromal cells (HESCs), which are independent of its anticoagulant effect. However, the accurate effects of heparin on the decidualization process remain unidentified. Here, we demonstrate that HESCs become dramatically resistant to oxidative stress upon decidualization, and we hypothesize a possible direct action of heparin on the decidualization of HESCs, which would lead to improved implantation. To test this hypothesis, we established primary HESC cultures and propagated them, and then we decidualized confluent cultures with 8-bromo-cAMP, with medroxyprogesterone acetate, and with or without heparin. We treated the cells with hydrogen peroxide (H2O2) as a source of reactive oxygen species (ROS). Adding heparin to decidualized HESCs induced prolactin secretion. Decidualized HESCs treated with heparin were prevented from undergoing apoptosis induced by oxidative stress. Heparin induced nuclear accumulation of the forkhead transcription factor FOXO1 and expression of its downstream target, the ROS scavenger superoxide dismutase 2. These results demonstrate that heparin-treated decidualized HESCs acquired further resistance to oxidative stress, suggesting that heparin may improve the implantation environment.