Nanjing Institute of Environmental Sciences, Ministry of Environmental Protection, Nanjing 210042, China; The College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 210009, China.
Nanjing Institute of Environmental Sciences, Ministry of Environmental Protection, Nanjing 210042, China.
Comp Biochem Physiol C Toxicol Pharmacol. 2018 Aug;210:44-56. doi: 10.1016/j.cbpc.2018.05.004. Epub 2018 May 16.
Bisphenol F (BPF) has become a predominant bisphenol contaminant in recent years. It has significant estrogenic properties in both in vivo and in vitro studies. We have previously studied the disrupting mechanisms of BPF on the hypothalamic-pituitary-gonadal axis of adult zebrafish. However, the effects of BPF exposure on development and sexual differentiation of zebrafish embryos/larvae remain unclear. To determine the effects of BPF on the critical stage of sex differentiation in zebrafish, zebrafish embryos/larvae were exposed to 1, 10, 100, and 1000 μg/L BPF from fertilization to 60 days post-fertilization (dpf). Developmental malformations were induced by exposure to BPF from 2 h post-fertilization (hpf), with a LC of 10,030 μg/L at 96 hpf and 9391 μg/L at 120 hpf. Long-term exposure during sex differentiation tended to result in a female sex ratio bias. Histological analyses at 60 dpf indicated that the development of ovo-testes and immature ovaries was induced by 100 and 1000 μg/L BPF. Homogenate testosterone levels decreased and 17β-estradiol levels increased in zebrafish in a concentration-dependent manner. BPF exposure suppressed gene expression of double sex, Mab3-related transcription factor 1(dmrt1), fushi tarazu factor 1d (ff1d), sry-box containing gene 9a (sox9a) and anti-Mullerian hormone (amh); induced expression of the forkhead box L2 transcription factor (foxl2), leading to increased expression of aromatase (cyp19a1a), which promoted production of estrogens, and further caused phenotypic feminization of zebrafish. These results suggest that developmental exposure to BPF has adverse effects on sexual differentiation, and the results were useful for a BPF risk assessment.
双酚 F（BPF）近年来已成为主要的双酚污染物。它在体内和体外研究中均具有显著的雌激素特性。我们之前研究了 BPF 对成年斑马鱼下丘脑-垂体-性腺轴的破坏机制。然而，BPF 暴露对斑马鱼胚胎/幼虫发育和性分化的影响尚不清楚。为了确定 BPF 对斑马鱼性别分化关键阶段的影响，从受精到 60 天孵化后（dpf），将斑马鱼胚胎/幼虫暴露于 1、10、100 和 1000μg/L 的 BPF 中。从受精后 2 小时（hpf）开始，BPF 暴露会引起发育畸形，96 hpf 时 LC 为 10,030μg/L，120 hpf 时 LC 为 9391μg/L。在性别分化期间进行的长期暴露往往会导致雌性性别比例偏向。60 dpf 的组织学分析表明，100 和 1000μg/L 的 BPF 诱导了卵睾和未成熟卵巢的发育。在浓度依赖性方式下，斑马鱼的匀浆睾酮水平降低，17β-雌二醇水平升高。BPF 暴露抑制了双性（dmrt1）、Fushi tarazu 因子 1d（ff1d）、Sry 盒基因 9a（sox9a）和抗缪勒管激素（amh）的基因表达；诱导了叉头框 L2 转录因子（foxl2）的表达，导致芳香酶（cyp19a1a）的表达增加，从而促进了雌激素的产生，并进一步导致了斑马鱼的表型雌性化。这些结果表明，发育过程中暴露于 BPF 会对性别分化产生不利影响，并且这些结果有助于进行 BPF 风险评估。
