摘要:
孕激素是广泛使用的高生物活性药物，其残留广泛存在于水环境中，对水生生物造成潜在威胁。本论文研究孕激素左炔诺孕酮(LNG)长期暴露对雄性斑马鱼的生殖毒性。将斑马鱼胚胎暴露于环境相关浓度的LNG(10, 33, 100 ng·L-1)至性成熟(受精后142 d)，得到100%的雄性斑马鱼。将得到的雄鱼与未暴露的雌鱼配对，结果发现100 ng·L-1 LNG处理组雄鱼使得未暴露雌鱼产卵的数量较对照组雄鱼使得未暴露雌鱼产卵的数量显著减少。33和100 ng·L-1处理组雄鱼与未暴露雌鱼配对所得子代在受精后7 d内的存活率较对照组雄鱼与未暴露雌鱼配对所得子代的存活率显著降低。33 ng·L-1 LNG显著升高总活力、活跃精子活力、平均路径速度、直线运动速度、曲线运动速度等精子活力参数，但其他浓度的LNG并不影响精子的活力。LNG在33和100 ng·L-1的浓度下显著降低雄鱼血浆中11-酮基睾酮(11-KT)的含量，且在3个浓度下均显著降低雄鱼血浆中雌二醇(E2)的含量，但对睾酮(T)无明显影响。此外，LNG暴露可干扰雄鱼大脑和精巢中孕激素受体(npr, mprα, mprβ)、雌激素受体(erα, erβ)以及雄激素受体(ar)的转录，可能通过这些受体途径参与生殖调控。研究结果表明环境相关浓度的左炔诺孕酮长期暴露可导致雄性斑马鱼的生殖内分泌干扰效应，并提示：仅雄鱼单独受孕激素暴露影响，也可能对鱼类种群的生殖产生深远影响。
Abstract:
Synthetic progestins are widely used pharmaceutical agents with high bioactivity, and their residuals are frequently detected in the aquatic environment, posing potential threats to the aquatic organisms. In the present study, we investigated the reproductive toxicity of progestin levonorgestrel (LNG) at environmentally relevant concentrations on zebrafish (Danio rerio). Embryos were exposed to LNG at environmentally relevant concentrations (10, 33 and 100 ng·L-1) and allowed to develop until sexual maturity (142 days post fertilization), and 100% males were induced in all the treatment groups. Egg production of unexposed female zebrafish was significantly reduced when paired with male zebrafish exposed to 100 ng·L-1 LNG, comparing with that of unexposed females paired with the control males. Survival rates of the offsprings from the unexposed females paired with males exposed to both 33 and 100 ng·L-1 LNG were significantly decreased within 7 days after fertilization, comparing with the survival rate of offsprings from the unexposed females paired with the control males. Semen samples were analyzed for total motility (TM), progressive motility (PM), velocity average path (VAP), velocity straight line (VSL), and velocity curvilinear (VCL). All those parameters showed significant increase in males exposed to 33 ng·L-1 when comparing with the control. However, no obvious changes were observed in other treatments. Plasma concentrations of 11-ketotestosterone (11-KT) or estradiol (E2) in males were significantly decreased after exposure to 33, 100 ng·L-1 LNG, or all concentrations of LNG, respectively, while no effects were observed on plasma concentrations of testosterone (T). Besides, LNG exposure disrupted the transcription of progesterone receptors (npr, mprα, mprβ), estrogen receptors (erα, erβ) and androgen receptor (ar) in the brain and testes, which may indicate the regulating roles in reproduction through these receptors. The present study suggests that long-term exposure to environmentally relevant concentrations of LNG could result in reproductive endocrine disruption in zebrafish. The results also indicate that male exposure to progestin alone may also have profound effects on reproduction in fish populations that inhabit in progestin-contaminated aquatic environments.
点击查看大图
下载:
