Department of MedicineUniversity of California San Diego, 9500 Gilman Drive 0605, La Jolla, California 92093-0605, USACSRC and BIMRCSan Diego State University, 5500 Campanile Drive, San Diego, California 92182-7720, USADepartment of MedicineMedical University of South Carolina, 135 Cannon Street, Suite 303 MSC 835, Charleston, South Carolina 29425, USA
Department of MedicineUniversity of California San Diego, 9500 Gilman Drive 0605, La Jolla, California 92093-0605, USACSRC and BIMRCSan Diego State University, 5500 Campanile Drive, San Diego, California 92182-7720, USADepartment of MedicineMedical University of South Carolina, 135 Cannon Street, Suite 303 MSC 835, Charleston, South Carolina 29425, USADepartment of MedicineUniversity of California San Diego, 9500 Gilman Drive 0605, La Jolla, California 92093-0605, USACSRC and BIMRCSan Diego State University, 5500 Campanile Drive, San Diego, California 92182-7720, USADepartment of MedicineMedical University of South Carolina, 135 Cannon Street, Suite 303 MSC 835, Charleston, South Carolina 29425, USA
J Mol Endocrinol. 2014 Jun;52(3):R241-56. doi: 10.1530/JME-13-0219.
Endocrine-disrupting chemicals (EDCs), including plasticizers, pesticides, detergents, and pharmaceuticals, affect a variety of hormone-regulated physiological pathways in humans and wildlife. Many EDCs are lipophilic molecules and bind to hydrophobic pockets in steroid receptors, such as the estrogen receptor and androgen receptor, which are important in vertebrate reproduction and development. Indeed, health effects attributed to EDCs include reproductive dysfunction (e.g. reduced fertility, reproductive tract abnormalities, and skewed male:female sex ratios in fish), early puberty, various cancers, and obesity. A major concern is the effects of exposure to low concentrations of endocrine disruptors in utero and post partum, which may increase the incidence of cancer and diabetes in adults. EDCs affect transcription of hundreds and even thousands of genes, which has created the need for new tools to monitor the global effects of EDCs. The emergence of massive parallel sequencing for investigating gene transcription provides a sensitive tool for monitoring the effects of EDCs on humans and other vertebrates, as well as elucidating the mechanism of action of EDCs. Zebrafish conserve many developmental pathways found in humans, which makes zebrafish a valuable model system for studying EDCs, especially on early organ development because their embryos are translucent. In this article, we review recent advances in massive parallel sequencing approaches with a focus on zebrafish. We make the case that zebrafish exposed to EDCs at different stages of development can provide important insights on EDC effects on human health.
内分泌干扰化学物质（EDCs），包括增塑剂、农药、清洁剂和药品，会影响人类和野生动物中多种受激素调节的生理途径。许多 EDCs 是亲脂性分子，会与甾体受体（如雌激素受体和雄激素受体）中的疏水性口袋结合，这些受体在脊椎动物的繁殖和发育中非常重要。事实上，归因于 EDCs 的健康影响包括生殖功能障碍（例如生育能力降低、生殖道异常和鱼类中雄性与雌性比例的偏差）、性早熟、各种癌症和肥胖症。一个主要关注点是在子宫内和产后暴露于低浓度内分泌干扰物的影响，这可能会增加成年人患癌症和糖尿病的几率。EDCs 会影响数百甚至数千个基因的转录，这就需要新的工具来监测 EDCs 的全球影响。大规模平行测序技术用于研究基因转录的出现为监测 EDCs 对人类和其他脊椎动物的影响以及阐明 EDCs 的作用机制提供了一种敏感的工具。斑马鱼保留了许多在人类中发现的发育途径，这使得斑马鱼成为研究 EDCs 的有价值的模型系统，特别是在早期器官发育方面，因为它们的胚胎是半透明的。在本文中，我们重点介绍了斑马鱼的大规模平行测序方法的最新进展。我们认为，在不同发育阶段暴露于 EDCs 的斑马鱼可以为 EDC 对人类健康的影响提供重要的见解。
