DISSERTATION RESEARCH: Behavioral and Reproductive Implications of Nanomaterial and Synthetic Estrogen Co-Exposures in Fish

人造纳米材料(NMS)的潜在应用数量在世界各地呈指数级增长，而没有相应的研究无意间或有目的地排放到环境中可能产生的后果。鱼类和其他水生生物生活在NMS可能被处置的水体中。越来越多的证据表明，根据其成分、大小或表面官能化程度，一些NMS可能会影响鱼类健康。这项研究的目的是评估NMS是否可以干扰鱼类的繁殖行为。这个项目很重要，因为行为的改变可能会对遗传和种群产生毁灭性的影响。这里提出的研究将填补在理解可能释放到环境中的工程化NMS的生态毒理学影响方面的一个很大空白。最终，这样的研究将通过明确定义使NMS具有生物活性的特征来影响NMS的发展，这些特征应该在制造和未来的环境监管政策中得到考虑。本论文研究的总体目标是，通过灌胃将NMS口服进入鱼类可以通过肠道进入血液，然后分配到器官中，在那里它们可以进一步影响细胞机制，包括类固醇的生成。口服剂量的量子点穿过肠道上皮，积聚在包括性腺在内的各种组织中，这表明它们可能对组织功能有深远的影响。这个项目将具体解决一个新的假设，即NMS能够干扰愚蠢的小鱼的繁殖行为。已知内源或外源类固醇激素控制鱼类的繁殖行为。要测试的具体假设是(A)功能化的量子点将内化到睾丸中，干扰类固醇的生成并改变男性的生殖行为，以及(B)单壁碳纳米管将结合和隔离外源添加的乙烯基雌二醇，并抑制男性行为的女性化。这些假说将通过体内研究来确定NMS和环境雌激素(EE)对愚头鱼Pimephales proelas的基因表达和竞争性繁殖行为的相互作用。预期的结果是：(1)单壁碳纳米管将降低EE的生物利用度，并最终改变筑巢和防御行为；(2)量子点将导致FHM的生殖行为缺陷；(3)EE联合暴露将加剧量子点产生的影响。

The number of potential applications for manufactured nanomaterials (NMs) is growing exponentially around the world, without concomitant research into the possible consequences of inadvertent or purposeful releases into the environment. Fish and other aquatic organisms reside in bodies of water where NMs are likely to be disposed. A growing body of evidence suggests that some NMs, depending on their composition, size or surface functionalization, can affect fish health. The goal of this study is to evaluate if NMs can interfere with fish reproductive behavior. This project is important because alterations in behavior can have devastating genetic and population effects. The research proposed here will fill a large gap in the understanding of the ecotoxicological implications of engineered NMs that may be released into the environment. Ultimately, studies like this one will influence NM development by clearly defining the characteristics that make NMs bio-active and that should be considered in manufacturing and future environmental regulatory policies.The overarching goal of this thesis research is that NMs introduced into fish orally through gavage can penetrate through the intestine into the blood stream and then partition into organs where they can further impact with cellular mechanisms including steriodogenesis. Orally dosed quantum dots (QDs) cross the gut epithelium and accumulate in various tissues including the gonads, suggesting they may have profound effects on tissue function. This project will specifically address a new hypothesis that NMs are able to interfere with reproductive behaviors of fathead minnows. It is known that endogenous or exogenous steroid hormones control reproductive behavior of fish. The specific hypotheses to be tested are (A) that functionalized QDs will be internalized into testis and interfere with steroidogenesis and alter male reproductive behavior, and (B) that single walled carbon nanotubes will bind and sequester exogenously added ethinylestradiol and inhibit feminization of male behavior. These hypotheses will be tested using in vivo studies to determine the interactions between NMs and environmental estrogen (EE) on gene expression and competitive reproductive behavior in fathead minnows, Pimephales promelas. The expected outcomes are that (1) SWCNTs will reduce EE bioavailability and ultimately alter nest holding and defending behavior, (2) QDs will cause reproductive behavioral deficits in FHMs, and (3) that the effects produced by QDs will be exacerbated by EE co-exposure.