Aromatase modulation alters gonadal differentiation in developing zebrafish (Danio rerio)
Aromatase modulation alters gonadal differentiation in developing zebrafish (Danio rerio)
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DOI：
10.1016/j.aquatox.2003.10.008
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发表时间：
2004-04-14
影响因子：
4.5
通讯作者：
Segner, H
中科院分区：
文献类型：
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作者：
Fenske, M;Segner, H
本研究调查了斑马鱼 (Danio rerio) 的性腺性别分化是否对干扰细胞色素 P450 芳香酶 (P450arom) 的化合物敏感。在性腺分化期间用非甾体芳香酶抑制剂法屈唑或 17α-甲基睾酮 (MT) 处理斑马鱼，改变了性腺形态分化并改变了 P450arom 基因 (CYP19) 的表达模式。在受精后 (pf) 第 35 天至 71 天之间应用法屈唑（500 微克/克食物）导致 100% 男性化，即所有受检个体 (n = 40) 的性腺均显示睾丸形态。同时，通过半定量 RT-PCR 评估，法屈唑治疗抑制了性腺 CYP19A（性腺衍生的 CYP19 基因）mRNA 表达。在第 71 天终止法屈唑治疗并随后在对照条件下饲养斑马鱼直至第 161 天，所有个体的性腺仍然显示睾丸形态。然而，性腺 CYP19A 表达显示出二态性模式，22 条鱼中有 14 条具有与对照鱼睾丸中相似的低 CYP19A mRNA 水平，而 8 条鱼则显示出高水平的性腺 CYP19A mRNA。在性腺分化期间（产后第 35 至 71 天）进行 MT 处理（10 微克/升）会导致物候女性化，即所有检查的鱼（n = 28）都显示出卵巢性腺形态。虽然与对照鱼相比，性腺 CYP19A 表达受到抑制，但 71 日龄 MT 处理的鱼中，大脑 CYP19B（脑源性 CYP19 基因）mRNA 表达增加。这项研究的结果提供了证据，表明干扰 P450arom 系统的外源化合物能够破坏（甚至持续破坏）原生斑马鱼的性腺性别分化。 (C) 2003 Elsevier B.V. 保留所有权利。
This study investigated whether gonadal sex differentiation of zebrafish (Danio rerio) is susceptible to compounds that interfere with cytochrome P450 aromatase (P450arom). Treatment of zebrafish during the period of gonadal differentiation with either the non-steroidal aromatase inhibitor fadrozole or 17alpha-methyltestosterone (MT) changed gonad morphological differentiation and altered the pattern of P450arom gene (CYP19) expression. Application of fadrozole (500 mug/g of food) between days 35 and 71 post-fertilisation (pf) resulted in 100% masculinisation, i.e. the gonads of all individuals examined (n = 40) showed testicular morphology. At the same time, fadrozole treatment suppressed gonadal CYP19A (gonad-derived CYP19 gene) mRNA expression, as assessed by means of semi-quantitative RT-PCR. After termination of fadrozole treatment at day 71 pf and subsequent rearing of zebrafish under control conditions until 161 days pf, the gonads of all individuals still displayed testicular morphology. Gonadal CYP19A expression, however, showed a dimorphic pattern, with 14 out of 22 individuals having low CYP19A mRNA levels similar to those found in testes of control fish, while eight fish showed high, ovary-like levels of gonadal CYP19A mRNA. MT treatment (10 mug/l) during the period of gonadal differentiation (days 35 to 71 pf) resulted in phenological feminisation, i.e., all fish examined (n = 28) showed an ovarian gonadal morphology. While gonadal CYP19A expression was suppressed compared to control fish, cerebral CYP19B (brain-derived CYP19 gene) mRNA expression was increased in 71-day-old MT-treated fish. The results from this study provide evidence that exogenous compounds interfering with the P450arom system are able to disrupt, even persistently, gonadal sex differentiation of the protogynic zebrafish. (C) 2003 Elsevier B.V. All rights reserved.