Toxic effects of low doses of Bisphenol-A on human placental cells
Toxic effects of low doses of Bisphenol-A on human placental cells
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DOI：
10.1016/j.taap.2009.09.005
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发表时间：
2009-12-15
影响因子：
3.8
通讯作者：
Aris, Aziz
中科院分区：
文献类型：
--
作者：
Benachour, Nora;Aris, Aziz
人类每天都暴露在大量作为污染物存在的外来生物及其代谢物中。双酚a （BPA）广泛用于各种产品，包括婴儿奶瓶、食品储存容器、医疗设备和消费电子产品。因此，BPA是用于食品接触的聚碳酸酯中最常见的单体。母体血液、羊水、卵泡液、胎盘组织、脐带血和母体尿液中都含有这种工业产品。在这项研究中，我们研究了BPA浓度接近孕妇血清中发现的水平对人细胞滋养细胞（CTB）的毒性作用。这些细胞从新鲜胎盘中分离出来，暴露在BPA中24小时。我们的结果表明，通过M30抗体免疫荧光检测，极低剂量的BPA诱导细胞凋亡（2至3倍）。细胞膜损伤后，通过胞浆腺苷酸激酶（AK）活性评估细胞坏死（1.3 ~ 1.7倍）。通过实时荧光定量pcr和ELISA荧光检测，我们还发现BPA显著增加了肿瘤坏死因子α (tnf - α)基因的表达和蛋白质的分泌。此外，我们观察到诱导AK活化和tnf - α基因表达所需的BPA水平低于细胞凋亡或tnf - α蛋白排泄。我们的研究结果表明，胎盘细胞暴露于低剂量双酚a可能会造成有害影响，导致体内不良妊娠结局，如先兆子痫、宫内生长受限、早产和妊娠流产。(C) 2009爱思唯尔公司版权所有。
Humans are exposed daily to a great number of xenobiotics and their metabolites present as pollutants. Bisphenol-A (BPA) is extensively used in a broad range of products including baby bottles, food-storage containers, medical equipment, and consumer electronics. Thus, BPA is the most common monomer for polycarbonates intended for food contact. Levels of this industrial product are found in maternal blood, amniotic fluid, follicular fluid, placental tissue, umbilical cord blood, and maternal urine. In this study, we investigated toxic effects of BPA concentrations close to levels found in serum of pregnant women on human cytotrophoblasts (CTB). These cells were isolated from fresh placentas and exposed to BPA for 24 h. Our results showed that very low doses of BPA induce apoptosis (2 to 3 times) as assessed using M30 antibody immunofluorescent detection. and necrosis (1.3 to 1.7 times) as assessed through the cytosolic Adenylate Kinase (AK) activity after cell membrane damage. We also showed that BPA increased significantly the tumor-necrosis factor alpha (TNF-alpha) gene expression and protein excretion as measured by real-time RTPCR and ELISA luminescent test, respectively. Moreover, we observed that induction of AK activation and TNF-alpha gene expression require lower levels of BPA than apoptosis or TNF-alpha protein excretion. Our findings suggest that exposure of placental cells to low doses of BPA may cause detrimental effects, leading in vivo to adverse pregnancy outcomes such as preeclampsia, intrauterine growth restriction, prematurity and pregnancy loss. (C) 2009 Elsevier Inc. All rights reserved.