具有肾上腺发育毒性的外源化学物及其机制研究进展

Research progress in adrenal developmental toxicity and toxical mechanism of xenobiotics

妊娠期外源化学物暴露可引起子代肾上腺发育毒性,表现为形态及功能发育不良。具有肾上腺发育毒性的外源化学物主要包括环境毒物、药品和食品等,其毒性作用机制可能与外源化学物介导的表观遗传异常修饰、细胞自噬和内质网应激、代谢活化损伤等直接作用及糖皮质激素介导的间接效应有关。胎儿时期,外源化学物所致的肾上腺发育编程改变对子代健康具有重要影响,表现为成年后肾上腺局部低基础活性、高应激敏感性变化和"糖皮质激素-胰岛素样生长因子1轴"介导的肾上腺功能代偿性改变,进一步导致子代成年后多种慢性疾病易感。本文综述具有肾上腺发育毒性的外源性化学物种类及其毒性作用机制研究进展,阐述其远期危害,有利于建立肾上腺发育毒性评价系统。

Exposure to exogenous substances during pregnancy can cause adrenal developmental toxicity in offspring,characterized by morphological and functional dysplasia.The exogenous substances with adrenal developmental toxicity include environmental poisons,drugs and foods,and their mechanism of toxicity may be related to the direct effects of epigenetic modifications mediated by exogenous substances,autophagy,endoplasmic reticulum stress,metabolic injury and the indirect effects mediated by glucocorticoids.In utero,development programming changes of adrenal glands caused by exogenous substances have profound influence on offspring′s health,which can be manifested as low basic activity and high stress sensitivity in the adult adrenals and the compensatory changes in adrenal function mediated by the"glucocorticoid-insulin-like growth factor 1 axis",leaving the offspring more susceptible to many chronic diseases in adulthood.This article reviews the research progress in the types of toxins with adrenal developmental toxicity and their toxic mechanisms,and explains their long-term harm in order to facilitate the establishment of evaluation systems for adrenal developmental toxicity.