Liang Jiefeng, Liu Qian S, Ren Zhihua, Min Ke, Yang Xiaoxi, Hao Fang, Zhang Qing, Liu Qian, Zhou Qunfang, Jiang Guibin
State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, PR China; Sino-Danish College, University of Chinese Academy of Sciences, Beijing 100049, PR China; Shandong Key Laboratory of Environmental Processes and Health, School of Environmental Science and Engineering, Shandong University, Qingdao 266237, PR China.
State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, PR China.
Sci Total Environ. 2023 Apr 15;869:161793. doi: 10.1016/j.scitotenv.2023.161793. Epub 2023 Jan 23.
Increasing concerns have been raised on the health risks of parabens in the regard of their widespread applications and potential endocrine disrupting activities. In this study, four typical parabens, including methyl paraben (MeP), ethyl paraben (EtP), propyl paraben (PrP), and butyl paraben (BuP) were systematically investigated for their estrogen receptor- and steroid hormone-related endocrine disruptions using multi-level approaches. Paraben exposure promoted the proliferation of MCF-7 cells, increased the luciferase activity in MVLN cells, and induced the vitellogenin (vtg) expression in zebrafish larvae, showing the typical estrogenic effects. The in vitro protein assays further revealed that PrP and BuP could bind with two isoforms of estrogen receptors (ERs). The estrogenic activities of parabens were predicted to be positively correlated with their chemical structure complexity by using molecular docking analysis. Furthermore, the synthesis and secretion of estradiol (E2) and testosterone (T) were significantly disturbed in H295R cells and zebrafish larvae, which could be regulated by paraben-induced transcriptional disturbance in both in vitro steroidogenesis and in vivo hypothalamic-pituitary-gonadal (HPG) axis. Parabens could disturb the endocrine system by activating the ERs and disrupting the steroid hormone synthesis and secretion, suggesting their potential deleterious risks to the environment and human health.
由于对羟基苯甲酸酯的广泛应用及其潜在的内分泌干扰活性，人们对其健康风险的担忧日益增加。在本研究中，使用多层次方法系统地研究了四种典型的对羟基苯甲酸酯，包括对羟基苯甲酸甲酯（MeP）、对羟基苯甲酸乙酯（EtP）、对羟基苯甲酸丙酯（PrP）和对羟基苯甲酸丁酯（BuP）对雌激素受体和类固醇激素相关内分泌干扰的影响。对羟基苯甲酸酯暴露促进了MCF-7细胞的增殖，增加了MVLN细胞中的荧光素酶活性，并诱导了斑马鱼幼虫中的卵黄蛋白原（vtg）表达，显示出典型的雌激素效应。体外蛋白质分析进一步表明，PrP和BuP可以与两种雌激素受体（ERs）亚型结合。通过分子对接分析预测，对羟基苯甲酸酯的雌激素活性与其化学结构复杂性呈正相关。此外，在H295R细胞和斑马鱼幼虫中，雌二醇（E2）和睾酮（T）的合成和分泌受到显著干扰，这可能是由于对羟基苯甲酸酯在体外类固醇生成和体内下丘脑-垂体-性腺（HPG）轴中诱导的转录干扰所致。对羟基苯甲酸酯可通过激活ERs和破坏类固醇激素的合成与分泌来干扰内分泌系统，表明它们对环境和人类健康具有潜在的有害风险。
