基于生活环境、健康和疾病在分子水平上密切相关的核心理念,健康和疾病的发育起源(developmental origins of health and disease,DOHaD)理论为健康与疾病间的关联研究提供了全新视角。该理论通过多学科、多领域的知识互通,追溯不同的...基于生活环境、健康和疾病在分子水平上密切相关的核心理念,健康和疾病的发育起源(developmental origins of health and disease,DOHaD)理论为健康与疾病间的关联研究提供了全新视角。该理论通过多学科、多领域的知识互通,追溯不同的生活经历如何影响生命全过程中的健康和疾病风险。成人期疾病的敏感窗口期不再局限于妊娠前和妊娠期,分娩期至成年早期也成为暴露因素发挥作用的重要时段。母源性/父源性因素、环境因素、新生儿出生状况、儿童期代谢情况等能够通过影响表观遗传、代谢和免疫调控、氧化应激等,改变发育程序并对子代远期健康产生正向或负向影响。因此,为实现健康促进,需要同步推进早期生命阶段预防、后期随访及健康干预的关口前移,以期有效降低成年期疾病风险,提升生命全周期健康水平。综述DOHaD领域最新研究进展对阐明人类发展早期阶段发生的不良事件影响健康和疾病模式及发现有效干预措施具有积极意义。展开更多
There is consistent epidemiological evidence linking low birth weight, preterm birth and adverse fetal growth to an elevated risk of the metabolic syndrome (obesity, raised blood pressure, raised serum triglycerides, ...There is consistent epidemiological evidence linking low birth weight, preterm birth and adverse fetal growth to an elevated risk of the metabolic syndrome (obesity, raised blood pressure, raised serum triglycerides, lowered serum high-density lipoprotein cholesterol and impaired glucose tolerance or insulin resistance) and related disorders. This "fetal or developmental origins/programming of disease" concept is now well accepted but the "programming" mechanisms remain poorly understood. We reviewed the major evidence, implications and limitations of current hypotheses in interpreting developmental programming and discuss future research directions. Major current hypotheses to interpret developmental programming include: (1)thrifty phenotype; (2) postnatal accelerated or catchup growth; (3) glucocorticoid effects; (4) epigenetic changes; (5) oxidative stress; (6) prenatal hypoxia; (7) placental dysfunction; and (8) reduced stem cell number. Some hypothetical mechanisms (2, 4 and 8) could be driven by other upstream "driver" mechanisms. There is a lack of animal studies addressing multiple mechanisms simultaneously and a lack of strong evidence linking clinical outcomes to biomarkers of the proposed programming mechanisms in humans. There are needs for (1) experimental studies addressing multiple hypothetical mechanisms simultaneously; and (2) prospective pregnancy cohort studies linking biomarkers of the proposed mechanisms to clinical outcomes or surrogate biomarker endpoints. A better understanding of the programming mechanisms is a prerequisite for developing early life interventions to arrest the increasing epidemic of the metabolic syndrome, type 2 diabetes and other related disorders.展开更多
文摘基于生活环境、健康和疾病在分子水平上密切相关的核心理念,健康和疾病的发育起源(developmental origins of health and disease,DOHaD)理论为健康与疾病间的关联研究提供了全新视角。该理论通过多学科、多领域的知识互通,追溯不同的生活经历如何影响生命全过程中的健康和疾病风险。成人期疾病的敏感窗口期不再局限于妊娠前和妊娠期,分娩期至成年早期也成为暴露因素发挥作用的重要时段。母源性/父源性因素、环境因素、新生儿出生状况、儿童期代谢情况等能够通过影响表观遗传、代谢和免疫调控、氧化应激等,改变发育程序并对子代远期健康产生正向或负向影响。因此,为实现健康促进,需要同步推进早期生命阶段预防、后期随访及健康干预的关口前移,以期有效降低成年期疾病风险,提升生命全周期健康水平。综述DOHaD领域最新研究进展对阐明人类发展早期阶段发生的不良事件影响健康和疾病模式及发现有效干预措施具有积极意义。
基金Supported by a Research Grant from the Canadian Institutes of Health Research (CIHR), Institute of Nutrition, Metabolism and Diabetes (CIHR Grant # 79896 - Luo ZC)partly by a Clinical Epidemiology Junior Scholar Award from the Fonds de la Recherche en Santé du Québec (FRSQ) (Luo ZC)partly by a FRSQ Senior Scholar Award (Nuyt AM)
文摘There is consistent epidemiological evidence linking low birth weight, preterm birth and adverse fetal growth to an elevated risk of the metabolic syndrome (obesity, raised blood pressure, raised serum triglycerides, lowered serum high-density lipoprotein cholesterol and impaired glucose tolerance or insulin resistance) and related disorders. This "fetal or developmental origins/programming of disease" concept is now well accepted but the "programming" mechanisms remain poorly understood. We reviewed the major evidence, implications and limitations of current hypotheses in interpreting developmental programming and discuss future research directions. Major current hypotheses to interpret developmental programming include: (1)thrifty phenotype; (2) postnatal accelerated or catchup growth; (3) glucocorticoid effects; (4) epigenetic changes; (5) oxidative stress; (6) prenatal hypoxia; (7) placental dysfunction; and (8) reduced stem cell number. Some hypothetical mechanisms (2, 4 and 8) could be driven by other upstream "driver" mechanisms. There is a lack of animal studies addressing multiple mechanisms simultaneously and a lack of strong evidence linking clinical outcomes to biomarkers of the proposed programming mechanisms in humans. There are needs for (1) experimental studies addressing multiple hypothetical mechanisms simultaneously; and (2) prospective pregnancy cohort studies linking biomarkers of the proposed mechanisms to clinical outcomes or surrogate biomarker endpoints. A better understanding of the programming mechanisms is a prerequisite for developing early life interventions to arrest the increasing epidemic of the metabolic syndrome, type 2 diabetes and other related disorders.
