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首页> 外文学位 >Prostaglandins in the zebrafish ovary: Role, regulation, and modulation by environmental pharmaceuticals.
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Prostaglandins in the zebrafish ovary: Role, regulation, and modulation by environmental pharmaceuticals.

机译：斑马鱼卵巢中的前列腺素：环境药物的作用，调节和调节。

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摘要

A series of experiments in this thesis confirm that ovarian synthesis of prostaglandins (PG) is necessary for normal ovulation in the zebrafish, Danio rerio. Initial studies demonstrated reduced egg production by fish exposed to the PG-synthesis inhibitor, indomethacin. Subsequent studies showed that ovarian levels of the maturation inducing steroid 17alpha,20beta-dihydroxy-4-pregnen-3-one (17alpha,20beta-P) rise during oocyte maturation and PGF2alpha , rise near the time of ovulation and spawning. Peak levels of cytosolic phospholipase A2 (cPLA2) and cyclooxygenase-2 (COX-2) gene expression in follicles are observed just prior to ovulation. Collectively, these findings led to the hypothesis that gonadotropin and 17alpha,20beta-P induce ovulation in zebrafish through the activation of the arachidonic acid pathway and the subsequent rise in PG levels results in expulsion of the oocyte. Both cPLA2 and COX-2 expression was increased in the ovaries of fish exposed in vivo to human chorionic gonadotropin or 17alpha,20beta-P, which supports the hypothesis.;Recently, pharmaceuticals have been detected in the aquatic environment and there is concern that they may impact fish reproduction. My studies with zebrafish have shown reduced egg production in fish exposed to high concentrations of diclofenac (a non-steroidal anti-inflammatory drug; NSAID), fluoxetine (FLU; a selective serotonin reuptake inhibitor), ethinylestradiol (EE 2, a synthetic estrogen), and municipal effluent, but the underlying biochemical or molecular mechanisms differed. These studies showed that FLU decreased ovarian estradiol levels and the expression of aromatase and gonadotropin receptors (FSHr, LHr) in the ovary. EE2 exerted its effects on steroid biosynthesis whereas the NSAID affected PG synthesis. High levels of ammonia/nitrite confounded the results from the municipal effluent study because of dissimilarities in water quality among the treatments. Municipal effluent and FLU induced the expression of detoxification genes in the liver (CYP3A65) whereas EE2 reduced the expression of CYP1A1 and CYP3A65. Provided that sufficient treatment replication is included, the short-term exposure regime used in these toxicity studies is suitable for studying the potential reproductive effects of environmental pharmaceuticals in zebrafish.
机译：本论文中的一系列实验证实，卵巢合成前列腺素（PG）对于斑马鱼Danio rerio的正常排卵是必需的。初步研究表明，暴露于PG合成抑制剂吲哚美辛的鱼产卵量减少。随后的研究表明，在卵母细胞成熟过程中，卵巢成熟水平诱导类固醇17alpha，20beta-dihydroxy-4-pregnen-3-one（17alpha，20beta-P）升高，并且在排卵和产卵时升高。排卵前观察到卵泡中胞质磷脂酶A2（cPLA2）和环氧合酶2（COX-2）基因表达的峰值水平。总的来说，这些发现导致了这样的假设，即促性腺激素和17α，20β-P通过花生四烯酸途径的激活诱导斑马鱼排卵，随后PG水平的升高导致卵母细胞被排出。在体内暴露于人绒毛膜促性腺激素或17alpha，20beta-P的鱼的卵巢中cPLA2和COX-2的表达均增加，这支持了这一假设。；最近，在水生环境中检测到药物，人们担心它们会可能会影响鱼类繁殖。我对斑马鱼的研究表明，暴露于高浓度双氯芬酸（一种非甾体类抗炎药； NSAID），氟西汀（FLU；一种选择性5-羟色胺再摄取抑制剂），炔雌醇（EE 2，一种合成雌激素）的鱼类的产卵量减少。和市政污水，但其基本的生化或分子机制有所不同。这些研究表明，FLU可降低卵巢中的卵巢雌二醇水平以及芳香酶和促性腺激素受体（FSHr，LHr）的表达。 EE2对类固醇的生物合成产生影响，而NSAID影响了PG的合成。由于处理之间水质的差异，高含量的氨/亚硝酸盐使市政污水研究的结果感到困惑。市政污水和FLU诱导肝脏中的解毒基因（CYP3A65）的表达，而EE2降低CYP1A1和CYP3A65的表达。如果包括足够的治疗复制，则在这些毒性研究中使用的短期暴露方案适用于研究环境药物在斑马鱼中的潜在生殖作用。

著录项

  • 作者

    Lister, Andrea L.;

  • 作者单位

    University of Guelph (Canada).;

  • 授予单位 University of Guelph (Canada).;
  • 学科 Health Sciences Toxicology.;Biology Animal Physiology.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 229 p.
  • 总页数 229
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 毒物学（毒理学）;生理学;
  • 关键词

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