双酚B对斑马鱼性别分化的影响及作用机制
Effects and Mechanism of Bisphenol B on Sexual Differentiation of Zebrafish
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摘要: 双酚A（bisphenol A，BPA）是一种典型的内分泌干扰物，双酚B（bisphenol B，BPA）作为其替代物，使用量逐渐增多。一些研究表明，BPB也具有内分泌干扰效应，但是其对鱼类性别分化的影响尚无报道。本文将斑马鱼胚胎暴露于不同浓度的BPB中至受精后60 d（days post fertilization，dpf），研究BPB对斑马鱼性别分化的影响及可能的分子机制。结果表明，10、100和1 000 μg·L-1的BPB暴露导致斑马鱼性别比例向雌鱼偏离，雄鱼的精巢中发育出初级卵母细胞，并导致斑马鱼体内17β-雌二醇（17β-estradiol，E2）水平升高，睾酮（testosterone，T）水平降低，表明BPB对斑马鱼具有雌激素效应。从基因水平探讨这2种物质导致斑马鱼雌性化的原因，发现BPB使卵巢分化相关基因foxl2的表达水平上升，精巢分化相关基因dmrt1、amh和sox9a表达水平降低，并进一步提高了芳香化酶基因cyp19a1a的转录水平，促进E2的合成，导致斑马鱼的性别分化过程发生异常。Abstract: Bisphenol B (BPB) has been increasingly used as an alternative to bisphenol A (BPA) owing to BPA’s endocrine disrupting effects. Some researches indicate that BPB exhibits similar adverse effects, while data of toxicity on sexual differentiation and sex determination are still limited. In the present study, zebrafish embryos were exposed to BPB from 2 hours post fertilization (hpf) to 60 days post fertilization (dpf) to investigate the effects of BPB on sex differentiation of zebrafish. The results indicated that 10, 100 and 1 000μ g·L-1 BPB 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 were induced. The concentration of testosterone (T) decreased while concentration of 17β-estradiol (E2) increased in a concentration-dependent manner, indicating BPB has estrogen activity. BPB exposure induced expression of foxl2, which is crucial for the ovarian development, and suppressed gene expression of dmrt1, amh and sox9a, which are crucial for the testicular development. Variation of these genes leaded to increased expression of cyp19a1a, which promoted production of estrogens, and further caused phenotypic feminization.
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Key words:
- bisphenol B /
- zebrafish /
- endocrine disrupting effects /
- sex determination /
- gonad development
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