Isolating causative agents in complex mixtures

在全球范围内，已报道了与各种新出现的令人关注的污染物（例如药品）有关的对鱼类发育和繁殖的微妙影响。近年来，在受市政、工业（如纸浆厂）和农业活动影响的流域，广泛报道了双性鱼（如雄性生殖组织中的卵）的发生率。在安大略省南部的格兰德河，非常高水平的双性（睾丸中的初级卵母细胞）以及鱼类种群的变化（性腺大小减小）和社区反应（相对物种丰度）与城市污水排放有关。虽然一些污染物已被记录在废水流出物中，通过与雌激素受体结合改变鱼类的内分泌功能，但它们不能完全解释在接收环境中的观察结果。最近的研究表明，许多其他化学物质和机制也可能有助于鱼的双性表达和生殖性能的改变。这些因素包括阻断雄激素受体的化合物（例如几种杀虫剂、工业污染物）和栖息地条件，如氧气减少（缺氧），这会改变对发育和繁殖至关重要的天然激素的正常合成和代谢。造成这些变化的化学品或条件通常与非常复杂的混合物有关，使风险评估和管理非常不确定。目前的提案将通过开发技术来分离和识别格兰德河流域城市污水和农业径流中的潜在致病污染物来探索这一问题。控制这些化学物质的命运和生物利用度的机制，以及它们相互作用改变控制性能的关键生物功能的能力，将被建模。将根据对流域处理基础设施的投资，审查野生鱼类中这些已查明的化学物质与整个生物体和种群水平的影响的关系，特别是雌雄之间的影响。

Subtle effects on the development and reproduction of fish have been reported globally associated with a variety of emerging contaminants of concern (e.g. pharmaceuticals). In recent years, the incidence of intersex, (e.g. eggs in male reproductive tissue) in fish has been reported widely in watersheds affected by municipal, industrial (e.g. pulp mill) and agricultural activities. In the Grand River in southern Ontario, very high levels of intersex (primary oocytes in testes) as well as changes in fish population (reduced gonad size) and community responses (relative species abundance) have been associated with municipal wastewater outfalls. Although a number of contaminants have been documented in wastewater effluents that alter endocrine function in fish through binding to the estrogen receptor, they cannot fully explain the observations in the receiving environment. Recent studies have suggested that a number of other chemicals and mechanisms may also contribute to the expression of intersex and altered reproductive performance in fish. These include compounds that block the androgen receptor (e.g. several pesticides, industrial contaminants) and habitat conditions such as reduced oxygen (hypoxia) that alter the normal synthesis and metabolism of natural hormones that are critical in development and reproduction. The chemicals or conditions responsible for these changes are usually associated with very complex mixtures making risk assessment and management very uncertain. The current proposal will explore this issue by developing techniques to isolate and identify potential causative contaminants in both municipal effluents and agricultural runoff in the Grand River watershed. The mechanisms controlling fate and bioavailability of these chemicals, as well as their ability to interact to alter critical biological functions controlling performance, will be modelled. The relationship of these identified chemicals in wild fish to the expression of whole organism and population level effects, especially intersex, will be examined in response to investments in treatment infrastructure in the watershed.