The developmental origins of health and diseases(DOHaD)is a concept stating that adverse intrauterine environments contribute to the health risks of offspring.Since the theory emerged more than 30 years ago,many epide...The developmental origins of health and diseases(DOHaD)is a concept stating that adverse intrauterine environments contribute to the health risks of offspring.Since the theory emerged more than 30 years ago,many epidemiological and animal studies have confirmed that in utero exposure to environmental insults,including hyperglycemia and chemicals,increased the risk of developing noncommunicable diseases(NCDs).These NCDs include metabolic syndrome,type 2 diabetes,and complications such as diabetic cardiomyopathy.Studying the effects of different environmental insults on early embryo development would aid in understanding the underlying mechanisms by which these insults promote NCD development.Embryonic stem cells(ESCs)have also been utilized by researchers to study the DOHaD.ESCs have pluripotent characteristics and can be differentiated into almost every cell lineage;therefore,they are excellent in vitro models for studying early developmental events.More importantly,human ESCs(hESCs)are the best alternative to human embryos for research because of ethical concerns.In this review,we will discuss different maternal conditions associated with DOHaD,focusing on the complications of maternal diabetes.Next,we will review the differentiation protocols developed to generate different cell lineages from hESCs.Additionally,we will review how hESCs are utilized as a model for research into the DOHaD.The effects of environmental insults on hESC differentiation and the possible involvement of epigenetic regulation will be discussed.展开更多
Traditional Chinese Medicine (TCM) is the medical science based on theories and practicing experience of traditional Chinese medicine to study transferring principles of health and sickness,as well as prevention, diag...Traditional Chinese Medicine (TCM) is the medical science based on theories and practicing experience of traditional Chinese medicine to study transferring principles of health and sickness,as well as prevention, diagnosis,treatment,rehabilitation and healthcare.TCM is marked with its long history of development,integrated theory system and abundant practicing experience.展开更多
I.The History of the Drafting of the Universal Declaration of Human Rights:the Position and Role of the UN Economic and Social Council and the General Assembly of the United Nations should not be Ignored The reason fo...I.The History of the Drafting of the Universal Declaration of Human Rights:the Position and Role of the UN Economic and Social Council and the General Assembly of the United Nations should not be Ignored The reason for me to use the term "source"in the discussion on the right to subsistence展开更多
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
The ways in which epigenetic modifications fix the effects of early environmental events,ensuring sustained responses to transient stimuli,which result in modified gene expression patterns and phenotypes later in life...The ways in which epigenetic modifications fix the effects of early environmental events,ensuring sustained responses to transient stimuli,which result in modified gene expression patterns and phenotypes later in life,is a topic of considerable interest.This review focuses on recently discovered mechanisms and calls into question prevailing views about the dynamics,position and functions of epigenetic marks.Most epigenetic studies have addressed the long-term effects on a small number of epigenetic marks,at the global or individual gene level,of environmental stressors in humans and animal models.In parallel,increasing numbers of studies based on high-throughput technologies and focusing on humans and mice have revealed additional complexity in epigenetic processes,by highlighting the importance of crosstalk between the different epigenetic marks.A number of studies focusing on the developmental origin of health and disease and metabolic programming have identified links between early nutrition,epigenetic processes and long-term illness.The existence of a self-propagating epigenetic cycle has been demonstrated.Moreover,recent studies demonstrate an obvious sexual dimorphism both for programming trajectories and in response to the same environmental insult.Despite recent progress,we are still far from understanding how,when and where environmental stressors disturb key epigenetic mechanisms.Thus,identifying the original key marks and their changes throughout development during an individual's lifetime or over several generations remains a challenging issue.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The developmental origins of health and diseases(DOHaD)is a concept stating that adverse intrauterine environments contribute to the health risks of offspring.Since the theory emerged more than 30 years ago,many epidemiological and animal studies have confirmed that in utero exposure to environmental insults,including hyperglycemia and chemicals,increased the risk of developing noncommunicable diseases(NCDs).These NCDs include metabolic syndrome,type 2 diabetes,and complications such as diabetic cardiomyopathy.Studying the effects of different environmental insults on early embryo development would aid in understanding the underlying mechanisms by which these insults promote NCD development.Embryonic stem cells(ESCs)have also been utilized by researchers to study the DOHaD.ESCs have pluripotent characteristics and can be differentiated into almost every cell lineage;therefore,they are excellent in vitro models for studying early developmental events.More importantly,human ESCs(hESCs)are the best alternative to human embryos for research because of ethical concerns.In this review,we will discuss different maternal conditions associated with DOHaD,focusing on the complications of maternal diabetes.Next,we will review the differentiation protocols developed to generate different cell lineages from hESCs.Additionally,we will review how hESCs are utilized as a model for research into the DOHaD.The effects of environmental insults on hESC differentiation and the possible involvement of epigenetic regulation will be discussed.
文摘Traditional Chinese Medicine (TCM) is the medical science based on theories and practicing experience of traditional Chinese medicine to study transferring principles of health and sickness,as well as prevention, diagnosis,treatment,rehabilitation and healthcare.TCM is marked with its long history of development,integrated theory system and abundant practicing experience.
文摘I.The History of the Drafting of the Universal Declaration of Human Rights:the Position and Role of the UN Economic and Social Council and the General Assembly of the United Nations should not be Ignored The reason for me to use the term "source"in the discussion on the right to subsistence
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 Grants from INRA,INSERM (ATC-Nutrition,PRNH)Association Franaise des Diabétiques+3 种基金the Institut Benjamin Delessertthe Fondation Coeur et Artères (FCA N° 05-T4)the Agence Nationale pour la Recherche (ANR 06-PNRA-022-01)Contrat Cadre d’Aide au Projet d’Innova-tion Stratégique Industrielle "IT-Diab"OSEO-ISI (ISI IT-DIAB-18/12/2008)
文摘The ways in which epigenetic modifications fix the effects of early environmental events,ensuring sustained responses to transient stimuli,which result in modified gene expression patterns and phenotypes later in life,is a topic of considerable interest.This review focuses on recently discovered mechanisms and calls into question prevailing views about the dynamics,position and functions of epigenetic marks.Most epigenetic studies have addressed the long-term effects on a small number of epigenetic marks,at the global or individual gene level,of environmental stressors in humans and animal models.In parallel,increasing numbers of studies based on high-throughput technologies and focusing on humans and mice have revealed additional complexity in epigenetic processes,by highlighting the importance of crosstalk between the different epigenetic marks.A number of studies focusing on the developmental origin of health and disease and metabolic programming have identified links between early nutrition,epigenetic processes and long-term illness.The existence of a self-propagating epigenetic cycle has been demonstrated.Moreover,recent studies demonstrate an obvious sexual dimorphism both for programming trajectories and in response to the same environmental insult.Despite recent progress,we are still far from understanding how,when and where environmental stressors disturb key epigenetic mechanisms.Thus,identifying the original key marks and their changes throughout development during an individual's lifetime or over several generations remains a challenging issue.
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.
