Department of Gynecology and Obstetrics, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, P.R. China.
Int J Mol Med. 2021 Aug;48(2). doi: 10.3892/ijmm.2021.4983. Epub 2021 Jun 16.
The developmental origins of health and disease concept illustrates that exposure in early life to various factors may affect the offspring's long‑term susceptibility to disease. During development, the nervous system is sensitive and vulnerable to the environmental insults. Polychlorinated biphenyls (PCBs), which are divided into dioxin‑like (DL‑PCBs) and non‑dioxin‑like PCBs (NDL‑PCBs), are synthetic persistent environmental endocrine‑disrupting chemicals. The toxicological mechanisms of DL‑PCBs have been associated with the activation of the aryl hydrocarbon receptor and NDL‑PCBs have been associated with ryanodine receptor‑mediated calcium ion channels, which affect neuronal migration, promote dendritic growth and alter neuronal connectivity. In addition, PCB accumulation in the placenta destroys the fetal placental unit and affects endocrine function, particularly thyroid hormones and the dopaminergic system, leading to neuroendocrine disorders. However, epidemiological investigations have not achieved a consistent result in different study cohorts. The present review summarizes the epidemiological differences and possible mechanisms of the effects of intrauterine PCB exposure on neurological development.
健康与疾病的发育起源概念表明,生命早期接触各种因素可能会影响后代对疾病的长期易感性。在发育过程中,神经系统对外界环境的刺激非常敏感和脆弱。多氯联苯(PCBs)可分为类二噁英(DL-PCBs)和非类二噁英(NDL-PCBs),它们是合成的持久性环境内分泌干扰化学物质。DL-PCBs 的毒理学机制与芳基烃受体的激活有关,而 NDL-PCBs 则与肌醇 1,4,5-三磷酸受体介导的钙离子通道有关,这些通道会影响神经元迁移、促进树突生长并改变神经元连接。此外,胎盘内 PCB 的积累会破坏胎儿胎盘单位,并影响内分泌功能,尤其是甲状腺激素和多巴胺能系统,导致神经内分泌紊乱。然而,不同研究队列的流行病学调查并未得出一致的结果。本综述总结了宫内 PCB 暴露对神经发育影响的流行病学差异及其可能的机制。