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首页> 外文学位 >Altered gene expression: A mechanism of reproductive toxicity in zebrafish (Danio rerio) exposed to benzo[a]pyrene.
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Altered gene expression: A mechanism of reproductive toxicity in zebrafish (Danio rerio) exposed to benzo[a]pyrene.

机译：基因表达改变：暴露于苯并[a] py的斑马鱼（斑马鱼）的生殖毒性机制。

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Although reductions in 17beta-estradiol and vitellogenin concentrations have been consistently observed in fish exposed to polycyclic aromatic hydrocarbons (PAHs), an understanding of the mechanism behind these changes has yet to be fully elucidated. The overall objective of the present research was to gain a better understanding of the effect of PAHs on transcription of genes involved in reproduction. The first objective of this research was to characterize the expression of follicle stimulating hormone receptor (FSH-R) and luteinizing hormone receptor (LH-R) and four key steroidogenic enzymes (P450-side chain cleavage (P450scc), P450 17alpha-Hydroxylase/17-20 lyase (P450c17), 20beta-Hydroxysteroid Dehydrogenase (20beta-HSD), P450-aromatase (P450arom)) in oocytes and whole ovaries at different stages of development in zebrafish to gain a better understanding of basic transcriptional regulation of ovarian development and maturation. All genes examined were differentially expressed in pre-, early, mid, and late-vitellogenic oocytes. In contrast, only LH-R was differentially expressed at 0, 48, and 96 hours after spawning. The results of the first experiment provided evidence that transcription of gonadotropin receptors and steroidogenic enzymes may be involved in regulating ovarian development and maturation.;Additional objectives of this project were (1) to determine if exposure to waterborne benzo[a]pyrene (B[a]P) (0, 1.5, or 3.0 mug/L) for 61 days affected reproduction in zebrafish and (2) to determine if waterborne exposure to B[a]P affected transcription of gonadotropins, steroidogenic enzymes, activin, vitellogenin, or estrogen receptor beta. A 50% and 48% reduction in total egg output was observed in the 1.5 mug/L and 3.0 mug/L treatments as compared to controls, respectively. Although not significant, there was a trend towards a decrease in the number of females that spawned following exposure to 3 mug B[a]P/L. Cytochrome P4501A1 (CYP1A1) mRNA was significantly increased in heads of B[a]P-exposed zebrafish whereas it was not elevated in livers of B[a]P-exposed fish. An increase in P450aromB, vitellogenin, and 20beta-HSD mRNA occurred in fish exposed to 3.0 mug B[a]P/L as compared to the controls. The results from this study demonstrate that reproduction in zebrafish is affected by waterborne exposure to B[a]P and that transcription of P450aromB, vitellogenin, and 20beta-HSD may be one mechanism of B[a]P-induced reproductive toxicity.
机译：尽管在暴露于多环芳烃（PAHs）的鱼类中始终观察到17β-雌二醇和卵黄蛋白原浓度的降低，但对于这些变化背后的机理的理解尚待充分阐明。本研究的总体目标是更好地了解PAHs对涉及生殖的基因转录的影响。这项研究的第一个目标是表征卵泡刺激素受体（FSH-R）和促黄体生成素受体（LH-R）以及四种关键的类固醇生成酶（P450侧链裂解（P450scc），P450 17alpha-羟化酶/斑马鱼卵母细胞和整个卵巢中处于不同发育阶段的17-20裂合酶（P450c17），20β-羟基类固醇脱氢酶（20beta-HSD），P450-芳香化酶（P450arom），以更好地了解卵巢发育和发育的基本转录调控成熟。检查的所有基因在前，早期，中期和晚期卵母细胞中均差异表达。相反，在产卵后0、48和96小时仅差异表达LH-R。第一个实验的结果提供了证据，证明促性腺激素受体和类固醇生成酶的转录可能参与调节卵巢的发育和成熟。该项目的其他目标是（1）确定是否暴露于水性苯并[a] B（B [ a] P）（0、1.5或3.0杯/升）持续61天会影响斑马鱼的繁殖，以及（2）确定水暴露于B [a] P是否会影响促性腺激素，类固醇生成酶，激活素，卵黄蛋白原或雌激素受体β。与对照组相比，在1.5杯/升和3.0杯/升的处理中，总产蛋量分别降低了50％和48％。尽管不显着，但有一种趋势，即暴露于3杯B [a] P / L后产卵的雌性数量减少。在暴露于B [a] P的斑马鱼的头部中，细胞色素P4501A1（CYP1A1）mRNA显着增加，而在暴露于B [a] P的鱼的肝脏中则没有升高。与对照组相比，暴露于3.0杯B [a] P / L的鱼中P450aromB，卵黄蛋白原和20beta-HSD mRNA的增加。这项研究的结果表明，斑马鱼的繁殖受到水暴露于B [a] P的影响，而P450aromB，卵黄蛋白原和20β-HSD的转录可能是B [a] P诱导的生殖毒性的一种机制。

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