Grilo Luís F, Tocantins Carolina, Diniz Mariana S, Gomes Rodrigo Mello, Oliveira Paulo J, Matafome Paulo, Pereira Susana P
CNC - Center for Neuroscience and Cell Biology, CIBB - Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal.
PhD Programme in Experimental Biology and Biomedicine (PDBEB), Institute for Interdisciplinary Research (IIIUC), University of Coimbra, Coimbra, Portugal.
Eur J Clin Invest. 2021 Oct;51(10):e13625. doi: 10.1111/eci.13625. Epub 2021 Jun 13.
Embryonic and foetal development are critical periods of development in which several environmental cues determine health and disease in adulthood. Maternal conditions and an unfavourable intrauterine environment impact foetal development and may programme the offspring for increased predisposition to metabolic diseases and other chronic pathologic conditions throughout adult life. Previously, non-communicable chronic diseases were only associated with genetics and lifestyle. Now the origins of non-communicable chronic diseases are associated with early-life adaptations that produce long-term dysfunction. Early-life environment sets the long-term health and disease risk and can span through multiple generations. Recent research in developmental programming aims at identifying the molecular mechanisms responsible for developmental programming outcomes that impact cellular physiology and trigger adulthood disease. The identification of new therapeutic targets can improve offspring's health management and prevent or overcome adverse consequences of foetal programming. This review summarizes recent biomedical discoveries in the Developmental Origins of Health and Disease (DOHaD) hypothesis and highlight possible developmental programming mechanisms, including prenatal structural defects, metabolic (mitochondrial dysfunction, oxidative stress, protein modification), epigenetic and glucocorticoid signalling-related mechanisms suggesting molecular clues for the causes and consequences of programming of increased susceptibility of offspring to metabolic disease after birth. Identifying mechanisms involved in DOHaD can contribute to early interventions in pregnancy or early childhood, to re-set the metabolic homeostasis and break the chain of subsequent events that could lead to the development of disease.
胚胎发育和胎儿发育是发育的关键时期，在此期间，多种环境信号决定成年后的健康与疾病状况。母体状况及不良的子宫内环境会影响胎儿发育，并可能使后代在成年后的整个生命过程中更易患代谢性疾病和其他慢性病理状况。以前，非传染性慢性病仅与遗传和生活方式有关。如今，非传染性慢性病的起源与导致长期功能障碍的早期生活适应有关。早期生活环境决定了长期的健康和疾病风险，且这种影响可能会延续多代。发育编程方面的最新研究旨在确定导致发育编程结果的分子机制，这些结果会影响细胞生理并引发成年疾病。识别新的治疗靶点可改善对后代健康的管理，并预防或克服胎儿编程的不良后果。本综述总结了健康与疾病发育起源（DOHaD）假说中近期的生物医学发现，并强调了可能的发育编程机制，包括产前结构缺陷、代谢（线粒体功能障碍、氧化应激、蛋白质修饰）、表观遗传和糖皮质激素信号相关机制，这些机制为出生后后代对代谢疾病易感性增加的编程原因和后果提供了分子线索。确定DOHaD中涉及的机制有助于在孕期或儿童早期进行早期干预，以重新建立代谢稳态并打破可能导致疾病发展的后续事件链。
