Mesquita Ana Raquel, Wegerich Yvonne, Patchev Alexandre V, Oliveira Mario, Leão Pedro, Sousa Nuno, Almeida Osborne F X
Life & Health Sciences Research Institute (ICVS), University of Minho, 4710-057 Braga, Portugal.
Semin Fetal Neonatal Med. 2009 Jun;14(3):130-5. doi: 10.1016/j.siny.2008.11.002. Epub 2008 Dec 12.
Epidemiological evidence links exposure to stress hormones during fetal or early postnatal development with lifetime prevalence of cardiac, metabolic, auto-immune, neurological and psychiatric disorders. This has led to the concept of 'developmental programming through stress'. Importantly, these effects (specifically, hypertension, hyperglycaemia and neurodevelopmental and behavioural abnormalities) can be reproduced by exposure to high glucocorticoid levels, indicating a crucial role of glucocorticoids in their causation. However, there can be important differences in outcome, depending on the exact time of exposure, as well as duration and receptor selectivity of the glucocorticoid applied. The mechanisms underlying programming by stress are still unclear but it appears that these environmental perturbations exploit epigenetic modifications of DNA and/or histones to induce stable modifications of gene expression. Programming of neuro- and behavioural development by glucocorticoids and stress are important determinants of lifetime health and should be a consideration when choosing treatments in obstetric and neonatal medicine.
流行病学证据表明,胎儿期或出生后早期发育过程中暴露于应激激素与心脏、代谢、自身免疫、神经和精神疾病的终生患病率相关。这导致了“通过应激进行发育编程”的概念。重要的是,这些影响(特别是高血压、高血糖以及神经发育和行为异常)可通过暴露于高糖皮质激素水平而重现,这表明糖皮质激素在其病因中起关键作用。然而,根据暴露的确切时间、所应用糖皮质激素的持续时间和受体选择性,结果可能存在重要差异。应激编程的潜在机制仍不清楚,但似乎这些环境扰动利用DNA和/或组蛋白的表观遗传修饰来诱导基因表达的稳定改变。糖皮质激素和应激对神经和行为发育的编程是终生健康的重要决定因素,在产科和新生儿医学中选择治疗方法时应予以考虑。