17β-Trenbolone exposure program metabolic dysfunction in larval medaka
17β-Trenbolone exposure program metabolic dysfunction in larval medaka
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17β-群勃龙暴露程序导致青鳉幼体代谢功能障碍
DOI：
10.1002/tox.22158
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发表时间：
2016
影响因子：
4.5
通讯作者：
Takashi Nishidaa
中科院分区：
文献类型：
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作者：
Satomi Mizukami-Murat;Katsuyuki Kishi-Kadota;Takashi Nishidaa
在这里，我们使用生理学和转录组学分析来评估17β-群勃龙（TB）对青鳉（Oryzias latipes）早期生命阶段代谢的影响。在生理实验中，性逆转率随TB浓度（2-100 ng/L）成比例地持续增加，在200 ng/L处理组中为100%（所有雄性）。在60和100纳克/升浓度下，结核病导致雌性性腺指数显著增加。这些雌性动物表现出肿胀的子宫，产卵量和生育力下降。观察到这些雌性动物的体重指数显著增加。浓度>20 ng/L的结核病会导致男性生育力下降，但未观察到其他影响。在转录组学（微阵列）实验中，幼虫暴露于TB长达7天。使用KEGG Orthology数据库的分析显示，显著上调的基因的主要类别包括“脂质代谢”和“萜类化合物和聚酮化合物的代谢”。在这些类别中突出显示了与通过甲羟戊酸途径的胆固醇生物合成相关的13个基因（包括羟甲基戊二酰辅酶A合酶、细胞质合酶和羊毛甾醇合酶）。逆转录-聚合酶链反应分析与微阵列结果一致，在基因表达变化的方向和幅度方面。在下调的基因中，在TB治疗中检测到与肥胖呈负相关的血管生成素样4和线粒体解偶联蛋白1。总之，研究结果表明，女性在生命早期暴露于结核病可能导致代谢功能障碍，包括肥胖和胆固醇合成中断。 © 2015 Wiley Periodicals，Inc.环境毒理学31：1539-1551，2016年。
Here, we used physiological and transcriptomic analyses to evaluate the effects of 17β‐trenbolone (TB) on metabolism during the early life stage of medaka (Oryzias latipes). In the physiological experiments, sex reversal rates increased continuously in proportion to TB concentrations (2–100 ng/L), and were 100% (all males) in the 200 ng/L treatment group. TB caused a significant increase in the gonadosomatic index of females at concentrations of 60 and 100 ng/L. These females exhibited swollen abdomens and decreased egg production and fertility. Significant increases were observed in the body mass index of these females. TB caused decreased fertility in males at concentrations >20 ng/L, but no other effects were observed. In the transcriptomic (microarray) experiments, larvae were exposed to TB for up to 7 d. Analyses using the KEGG Orthology Database revealed that predominant categories of significantly upregulated genes included “lipid metabolism” and “metabolism of terpenoids and polyketides.” Thirteen genes (including those for hydroxymethylglutaryl‐CoA synthase, cytoplasmic synthase, and lanosterol synthase) related to cholesterol biosynthesis via the mevalonate pathway were highlighted in these categories. Reverse transcriptase‐polymerase chain reaction analyses were consistent with the microarray results, in terms of the direction and magnitude of change to gene expression. Among the downregulated genes, angiopoietin‐like 4 and mitochondrial uncoupling protein 1, which are inversely correlated with obesity, were detected in the TB treatments. In conclusion, the results suggest that the exposure of females to TB during the early life stage may cause metabolic dysfunctions, including obesity and disrupted cholesterol synthesis. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1539–1551, 2016.