Abstract

Opportunities for the exposure of pregnant women to engineered nanoparticles have been increasing with the expanding use of these materials. Therefore, there are concerns that nanoparticles could have adverse effects on the establishment and maintenance of pregnancy. The effects of nanoparticles on the mother and fetus have been evaluated from this perspective, but there is still little knowledge about the effects on placentation and function acquisition, which are essential for the successful establishment and maintenance of pregnancy. Formation of the syncytiotrophoblast is indispensable for the acquisition of placental function, and impairment of syncytialization inevitably affects pregnancy outcomes. Here, we assessed the effect of nanoparticles on placental formation by using forskolin-treated BeWo cells, a typical in vitro model of trophoblast syncytialization. Immunofluorescence staining analysis revealed that silver nanoparticles with a diameter of 10 nm (nAg10) (at 0.156 µg/mL) significantly decreased the proportion of syncytialized BeWo cells, but gold nanoparticles with a diameter of 10 nm did not. Consistently, only nAg10 (at 0.156 µg/mL) significantly suppressed forskolin-induced elevation of CGB and SDC1 mRNA expression levels and human chorionic gonadotropin β production in a dose-dependent manner; these molecules are all markers of syncytialization. Besides, nAg10 significantly decreased the expression of ERVFRD-1, which encodes proteins associated with cell fusion. Moreover, nAg10 tended to suppress the expression of sFlt-1 e15a, a placental angiogenesis marker. Collectively, our data suggest that nAg10 could suppress formation of the syncytiotrophoblast and that induce placental dysfunction and the following poor pregnancy outcomes.

摘要

随着这些材料的广泛使用，孕妇接触工程纳米粒子的机会一直在增加。因此，有人担心纳米粒子可能对怀孕的建立和维持产生不利影响。纳米粒子对母亲和胎儿的影响已经从这个角度进行了评估，但对胎盘形成和功能获得的影响仍然知之甚少，而这对于成功建立和维持妊娠至关重要。合胞体滋养层的形成对于胎盘功能的获得是必不可少的，而合胞体化的损害不可避免地影响妊娠结局。在这里，我们通过使用毛喉素处理的 BeWo 细胞评估了纳米粒子对胎盘形成的影响，这是一种典型的滋养细胞合胞体化的体外模型。免疫荧光染色分析显示，直径为 10 nm (nAg10)（浓度为 0.156 µg/mL）的银纳米粒子显着降低了合胞体化 BeWo 细胞的比例，但直径为 10 nm 的金纳米粒子则没有。一致地，只有 nAg10（0.156 µg/mL）以剂量依赖性方式显着抑制毛喉素诱导的CGB和SDC1 mRNA 表达水平升高以及人绒毛膜促性腺激素 β 的产生；这些分子都是合胞体化的标志。此外，nAg10 显着降低了ERVFRD-1的表达, 它编码与细胞融合相关的蛋白质。此外，nAg10 倾向于抑制胎盘血管生成标志物 sFlt-1 e15a 的表达。总的来说，我们的数据表明 nAg10 可以抑制合体滋养细胞的形成，并导致胎盘功能障碍和以下不良妊娠结局。