Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland.
Pharmacol Rep. 2013;65(6):1632-9. doi: 10.1016/s1734-1140(13)71524-x.
Even though high doses of organic pollutants are toxic, relatively low concentrations have been reported to cause long-term alterations in functioning of individual organisms, populations and even next generations. Among these pollutants are dioxins, polychlorinated biphenyls, pesticides, brominated flame retardants, plasticizers (bisphenol A, nonylphenol, and phthalates) as well as personal care products and drugs. In addition to toxic effects, they are able to interfere with hormone receptors, hormone synthesis or hormone conversion. Because these chemicals alter hormone-dependent processes and disrupt functioning of the endocrine glands, they have been classified as endocrine-disrupting chemicals (EDCs). Because certain EDCs are able to alter neural transmission and the formation of neural networks, the term neural-disrupting chemicals has been introduced, thus implicating EDCs in the etiology of neurological disorders. Recently, public concern has been focused on the effects of EDCs on brain function, concomitantly with an increase in neuropsychiatric disorders, including autism, attention deficit and hyperactivity disorder as well as learning disabilities and aggressiveness. Several lines of evidence suggest that exposure to EDCs is associated with depression and could result in neural degeneration. EDCs act via several classes of receptors with the best documented mechanisms being reported for nuclear steroid and xenobiotic receptors. Low doses of EDCs have been postulated to cause incomplete methylation of specific gene regions in the young brain and to impair neural development and brain functions across generations. Efforts are needed to develop systematic epidemiological studies and to investigate the mechanisms of action of EDCs in order to fully understand their effects on wildlife and humans.
尽管高剂量的有机污染物具有毒性,但据报道,相对低浓度的污染物也会导致个体生物、种群甚至下一代的长期功能改变。这些污染物包括二恶英、多氯联苯、农药、溴化阻燃剂、增塑剂(双酚 A、壬基酚和邻苯二甲酸酯)以及个人护理产品和药物。除了毒性作用外,它们还能够干扰激素受体、激素合成或激素转化。由于这些化学物质改变了激素依赖的过程并破坏了内分泌腺的功能,因此它们被归类为内分泌干扰化学物质(EDCs)。由于某些 EDC 能够改变神经传递和神经网络的形成,因此引入了神经干扰化学物质这一术语,从而将 EDC 与神经发育障碍的病因联系起来。最近,人们越来越关注 EDC 对大脑功能的影响,同时神经精神障碍(包括自闭症、注意力缺陷多动障碍以及学习障碍和攻击性)的发病率也在增加。有几条证据表明,接触 EDC 与抑郁有关,并可能导致神经退化。EDC 通过几类受体发挥作用,其中核甾体和异生物质受体的作用机制得到了最好的证明。据推测,EDC 会导致年轻大脑中特定基因区域的不完全甲基化,并损害神经发育和跨代的大脑功能。需要努力开展系统的流行病学研究,并研究 EDC 的作用机制,以便充分了解它们对野生动物和人类的影响。