The elucidation of pathogenesis of developmental disorders induced by maternal nutritional condition in the fetal stage.

健康和疾病的发展起源：DOHaD范式是一个概念，在子宫内的经历重新编程了一个人在以后的生活中疾病的风险。在本研究中，我们采用小鼠模型，通过控制良好的实验程序来验证DOHaD理论在发育障碍中的应用。本研究采用AIN93G作为对照日粮和低蛋白日粮。出生后，检测后代的行为表型、大脑中的基因表达水平和基因启动子的基因组甲基化水平。在子宫内暴露于营养不良的后代表现出在家庭笼中的活动增加，与新物体的接触减少，社会调查减少。LP组成年后代mRNA表达模式和基因组甲基化模式与AIN93G组不同。然而，没有检测到基因表达水平和甲基化水平之间的直接相互作用。

The Developmental Origins of Health and Disease:DOHaD paradigm is a concept that in utero experiences reprogram an individual for later-in-life risk of diseases. In this study, we conducted experiments to validate the DOHaD theory in the developmental disorder with well-controlled experimental procedures using mouse model. We provided AIN93G as control diet and low-protein diet (LP) to pre-pregnant and pregnant females. After birth, behavioral phenotypes of offspring, gene expression level in brain, and genomic methylation levels in promoters of genes were examined. The offspring which were exposed to malnutrition in utero exhibited increased activity in the home cage, decreased contact to novel object, and decreased social investigation. The adult offspring of LP group group exhibited different pattern of mRNA expression and genomic methylation pattern relative to AIN93G group. However, no direct interaction between expression levels and methylation levels of genes were detected.