Coumestrol induces oxidative stress and impairs migration and embryonic growth.
Coumestrol induces oxidative stress and impairs migration and embryonic growth.
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DOI：
10.1530/rep-23-0017
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发表时间：
2023-07-01
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影响因子：
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通讯作者：
Caron KM
中科院分区：
文献类型：
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作者：
Marbrey MW;Douglas ES;Goodwin ER;Caron KM
虽然素食主义已经越来越受欢迎，特别是在孕妇中，植物雌激素在胎盘形成中的作用缺乏了解。细胞氧化应激和缺氧等因素以及香烟烟雾、植物雌激素和膳食补充剂等外部因素可以调节胎盘发育。在菠菜和大豆中发现了植物雌激素香豆雌酚，发现它不能穿过胎儿-胎盘屏障。由于香豆雌酚可能是一种有价值的补充剂或有效的毒素在怀孕期间，我们试图研究其在滋养层细胞功能和胎盘在小鼠妊娠中的作用。在用香豆雌酚处理滋养层细胞（HTR 8/SVneo）并进行RNA微阵列后，我们确定了3，079个基因发生了显著变化，其中最大的差异变化途径与氧化应激反应，细胞周期调控，细胞迁移和血管生成有关。经香豆雌酚处理后，滋养层细胞的迁移和增殖减少。此外，我们观察到香豆雌酚给药后活性氧蓄积增加。然后，我们通过在妊娠第0天至第12.5天用香豆雌酚或溶媒处理野生型妊娠小鼠，研究香豆雌酚在体内妊娠中的作用。人道处死后，香豆雌酚给药动物的胎仔和胎盘重量显著降低，胎盘显示成比例降低，形态学无明显变化。因此，我们得出结论，香豆雌酚损害滋养层细胞的迁移和增殖，导致活性氧的积累，并减少小鼠妊娠的胎儿和胎盘重量。胎盘的健康发育依赖于滋养层细胞迁移和减少氧化应激的存在。这篇文章描述了菠菜和大豆中的植物雌激素如何导致怀孕期间胎盘发育受损。
Although vegetarianism has grown in popularity especially among pregnant women, the effects of phytoestrogens in placentation lacks understanding. Factors such as cellular oxidative stress and hypoxia and external factors including cigarette smoke, phytoestrogens, and dietary supplements can regulate placental development. The isoflavone phytoestrogen coumestrol was identified in spinach and soy and was found to not cross the fetal-placental barrier. Since coumestrol could be a valuable supplement or potent toxin during pregnancy, we sought to examine its role in trophoblast cell function and placentation in a murine pregnancy. After treating trophoblast cells (HTR8/SVneo) with coumestrol and performing an RNA microarray, we determined 3,079 genes were significantly changed with the top differentially changed pathways related to the oxidative stress response, cell cycle regulation, cell migration, and angiogenesis. Upon treatment with coumestrol, trophoblast cells exhibited reduced migration and proliferation. Additionally, we observed increased reactive oxygen species accumulation with coumestrol administration. We then examined the role of coumestrol within an in vivo pregnancy by treating wildtype pregnant mice with coumestrol or vehicle from day 0 to 12.5 of gestation. Upon euthanasia, fetal and placental weights were significantly decreased in coumestrol treated animals with the placenta exhibiting a proportional decrease with no obvious changes in morphology. Therefore, we conclude that coumestrol impairs trophoblast cell migration and proliferation, causes accumulation of reactive oxygen species, and reduces fetal and placental weights in murine pregnancy. Healthy development of the placenta is dependent on trophoblast cell migration and reduced oxidative stress presence. This article describes how a phytoestrogen found in spinach and soy causes impaired placental development during pregnancy.