School of Natural and Environmental Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom of Great Britain and Northern Ireland.
Biological Sciences, University of Southampton, Southampton, United Kingdom of Great Britain and Northern Ireland.
J Endocrinol. 2019 Feb 22;242(1):T33-T49. doi: 10.1530/JOE-18-0676.
The concept emerging from Professor David Barker’s seminal research on the developmental origins of later-life disease has progressed in many directions since it was first published. One critical question being when during gestation might environment alter the developmental programme with such enduring consequences. Here, we review the growing consensus from clinical and animal research that the period around conception, embracing gamete maturation and early embryogenesis might be the most vulnerable period. We focus on four types of environmental exposure shown to modify periconceptional reproduction and offspring development and health: maternal overnutrition and obesity; maternal undernutrition; paternal diet and health; and assisted reproductive technology. These conditions may act through diverse epigenetic, cellular and physiological mechanisms to alter gene expression and cellular signalling and function in the conceptus affecting offspring growth and metabolism leading to increased risk for cardiometabolic and neurological disease in later life.
自教授大卫·巴克（David Barker）开创性地研究晚年疾病的发育起源以来，这一概念已经朝着许多方向发展。自从该研究首次发表以来，一个关键问题是，在妊娠期间，环境何时会以如此持久的方式改变发育计划。在这里，我们回顾了来自临床和动物研究的越来越多的共识，即受孕前后的时期，包括配子成熟和早期胚胎发生，可能是最脆弱的时期。我们重点关注四种已被证明可改变围孕期生殖和后代发育和健康的环境暴露类型：母体营养过剩和肥胖；母体营养不良；父亲的饮食和健康；以及辅助生殖技术。这些情况可能通过多种表观遗传、细胞和生理机制，改变胚胎中的基因表达和细胞信号转导及功能，影响后代的生长和代谢，导致晚年患心血管代谢和神经疾病的风险增加。
