Bisphenol A disrupts gene expression in human placental trophoblast cells

IF 2.8 4区 医学 Q2 REPRODUCTIVE BIOLOGY Reproductive toxicology Pub Date : 2015-06-01 DOI:10.1016/j.reprotox.2015.03.001
Chandrew Rajakumar , Haiyan Guan , David Langlois , Maria Cernea , Kaiping Yang
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引用次数: 42

Abstract

This study examined the effect of bisphenol A (BPA) on human placental gene expression using primary trophoblast cells as an in vitro model system. Trophoblast cells were isolated from human placentas at term, cultured and then exposed to environmentally relevant concentrations of BPA (0.1–2 μg/ml) for up to 24 h, after which levels of 11β-HSD2 mRNA, protein and activity were determined by standard radiometric conversion assay, western blotting, and qRT-PCR, respectively. The mRNA levels of several other prominent placental hormones/factors were also assessed by qRT-PCR. BPA dramatically increased levels of 11β-HSD2 activity, protein and mRNA in a time- and concentration-dependent manner (>4-fold). BPA also augmented aromatase, glucose transporter-1, CRH, and hCG mRNA levels while reducing the level of leptin mRNA. These findings demonstrate that BPA severely disrupts human placental gene expression in vitro, which suggests that exposure to BPA may contribute to altered placental function and consequent pregnancy complications.

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双酚A破坏人胎盘滋养细胞的基因表达
本研究以原代滋养层细胞为体外模型系统,研究了双酚A (BPA)对人胎盘基因表达的影响。从人胎盘中分离足月滋养细胞,培养后暴露于环境相关浓度的BPA (0.1 ~ 2 μg/ml)中24 h,分别采用标准辐射转换法、western blotting法和qRT-PCR法检测11β-HSD2 mRNA、蛋白和活性水平。其他几个重要的胎盘激素/因子的mRNA水平也通过qRT-PCR进行评估。BPA显著提高了11β-HSD2活性、蛋白和mRNA水平,并呈时间和浓度依赖性(4倍)。BPA还增加了芳香化酶、葡萄糖转运蛋白-1、CRH和hCG mRNA水平,同时降低了瘦素mRNA水平。这些发现表明,BPA在体外严重破坏人类胎盘基因表达,这表明暴露于BPA可能导致胎盘功能改变和随之而来的妊娠并发症。
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来源期刊
Reproductive toxicology
Reproductive toxicology 生物-毒理学
CiteScore
6.50
自引率
3.00%
发文量
131
审稿时长
45 days
期刊介绍: Drawing from a large number of disciplines, Reproductive Toxicology publishes timely, original research on the influence of chemical and physical agents on reproduction. Written by and for obstetricians, pediatricians, embryologists, teratologists, geneticists, toxicologists, andrologists, and others interested in detecting potential reproductive hazards, the journal is a forum for communication among researchers and practitioners. Articles focus on the application of in vitro, animal and clinical research to the practice of clinical medicine. All aspects of reproduction are within the scope of Reproductive Toxicology, including the formation and maturation of male and female gametes, sexual function, the events surrounding the fusion of gametes and the development of the fertilized ovum, nourishment and transport of the conceptus within the genital tract, implantation, embryogenesis, intrauterine growth, placentation and placental function, parturition, lactation and neonatal survival. Adverse reproductive effects in males will be considered as significant as adverse effects occurring in females. To provide a balanced presentation of approaches, equal emphasis will be given to clinical and animal or in vitro work. Typical end points that will be studied by contributors include infertility, sexual dysfunction, spontaneous abortion, malformations, abnormal histogenesis, stillbirth, intrauterine growth retardation, prematurity, behavioral abnormalities, and perinatal mortality.
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