孕期不良环境所致的子代多种疾病易感及其宫内编程机制

发布时间：2018-02-20 19:55

  本文关键词： 孕期不良环境 代谢综合征 下丘脑-垂体-肾上腺轴 表观遗传修饰 宫内编程　出处：《中国药理学与毒理学杂志》2017年01期 　论文类型：期刊论文

【摘要】：流行病学调查提示,孕期不良环境可引起子代低出生体重及其成年后多种慢性疾病的易感性增加,如代谢性疾病和神经精神性疾病等。然而,其发生机制尚未见系统的阐明。下丘脑-垂体-肾上腺(HPA)轴是机体应激相关的重要神经内分泌轴,在出生前、后的应激防御应答中发挥着重要的作用,也是宫内时期胎儿易受损伤的重要靶位。研究发现,孕期多种不良环境因素(包括外源环境和母体健康因素)可通过母体-胎盘-胎儿生物学单位,多途径地影响宫内胎儿发育,造成其出生后HPA轴发育编程改变及成年后多种慢性疾病易感。本综述结合本实验室的最新研究结果,综述了国际上有关孕期不良环境所致子代成年疾病易感的病因学和宫内编程机制的最新进展,提出宫内母源性糖皮质激素过暴露可引起子代宫内神经内分泌代谢编程改变,其核心是多器官糖皮质激素-胰岛素样生长因子1轴编程,表观遗传修饰异常参与其编程过程。
[Abstract]:Epidemiological studies have shown that adverse conditions during pregnancy can increase the susceptibility of offspring to low birth weight and multiple chronic diseases in adulthood, such as metabolic and neuropsychiatric disorders. The hypothalamus-pituitary-adrenal gland (HPA) axis is an important neuroendocrine axis related to stress, which plays an important role in the stress defense response before and after birth. It is also an important target for fetal vulnerability during intrauterine period. Studies have found that many adverse environmental factors during pregnancy (including exogenous environment and maternal health factors) can be passed through the mother-placenta-fetal biological unit. It affects intrauterine fetal development in many ways, resulting in postnatal HPA axis programming changes and susceptibility to multiple chronic diseases in adulthood. This review combined with the latest research results in our laboratory, This paper reviews the recent advances in the etiology and intrauterine programming mechanism of the susceptibility to adult diseases in offspring due to adverse pregnancy conditions. It is suggested that overexposure of maternal glucocorticoid may cause changes in neuroendocrine and metabolic programming in offspring. Its core is multi-organ glucocorticoid-insulin-like growth factor 1 axis programming, epigenetic modification is involved in its programming process.
【作者单位】： 武汉大学基础医学院药理学系;发育源性疾病湖北省重点实验室;
【基金】：国家自然科学基金(30830112);国家自然科学基金(81430089);国家自然科学基金(81220108026)~~
【分类号】：R714.2
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本文编号：1519892