Key Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province, College of Environment, Zhejiang University of Technology, Hangzhou, Zhejiang 310032, China.
College of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China.
Environ Sci Technol. 2020 Apr 7;54(7):4465-4474. doi: 10.1021/acs.est.9b07874. Epub 2020 Mar 13.
Despite the ubiquity of organophosphate flame retardants (OPFRs) metabolites in the biota, the endocrine disrupting potency has not been well examined. Herein, we chose three primary metabolites of OPFRs (BCIPP, BDCIPP, and DPHP) to investigate their potential endocrine disrupting effects by in vitro, in vivo, and in silico assays. Three metabolites were agonistic to rat estrogenic receptor alpha (ERα) and antagonists to human mineralocorticoid receptor (MR). BCIPP exerted endocrine disrupting effect contrasting to the negative response of its parental compound. It also poses the strongest binding capacity to ERα among the tested compounds. Both BCIPP and BDCIPP upregulated the genes encoded for estrogenic synthesis enzymes in H295R cells, including and . All three compounds stimulated the transcription of , whereas BCIPP and DPHP also triggered , encoding for corticoid production. BDCIPP inhibits genes for progesterone synthesis including , , and . The induction of mortality and low hatchability of zebrafish embryo were ranked as BCIPP ≥ BDCIPP > DPHP. All compounds lead to malformation of zebrafish larvae. Both of the hypothalamic-pituitary-adrenocortical and hypothalamic-pituitary-gonadal axes were disrupted, with the highest impact by BCIPP. Altogether, the data clarified OPFRs metabolites may produce comparable or even higher endocrine disrupting effects than OPFRs.
尽管有机磷酸酯阻燃剂 (OPFRs) 代谢物在生物群中普遍存在，但它们的内分泌干扰潜力尚未得到充分研究。在此，我们选择了三种 OPFRs 的主要代谢物 (BCIPP、BDCIPP 和 DPHP)，通过体外、体内和计算方法研究它们潜在的内分泌干扰作用。这三种代谢物均对大鼠雌激素受体 alpha (ERα) 具有激动作用，对人矿物皮质激素受体 (MR) 具有拮抗作用。BCIPP 表现出与母体化合物相反的内分泌干扰作用。它还对 ERα 具有最强的结合能力。BCIPP 和 BDCIPP 均能上调 H295R 细胞中编码雌激素合成酶的基因，包括 和 。这三种化合物均能刺激 基因的转录，而 BCIPP 和 DPHP 也能触发 基因的转录，编码皮质激素的产生。BDCIPP 抑制包括 、 和 在内的孕激素合成基因。斑马鱼胚胎死亡率和孵化率的降低程度依次为 BCIPP≥BDCIPP>DPHP。所有化合物均导致斑马鱼幼虫畸形。下丘脑-垂体-肾上腺皮质轴和下丘脑-垂体-性腺轴均受到干扰，BCIPP 的影响最大。总的来说，这些数据表明 OPFRs 代谢物可能产生与 OPFRs 相当甚至更高的内分泌干扰作用。
