Pereira Troy J, Moyce Brittany L, Kereliuk Stephanie M, Dolinsky Vernon W
University of Manitoba, Department of Pharmacology and Therapeutics, Children's Hospital Research Institute of Manitoba, 715 McDermot Avenue, Winnipeg, MB R3E 3P4, Canada.
Biochem Cell Biol. 2015 Oct;93(5):438-51. doi: 10.1139/bcb-2014-0141. Epub 2014 Dec 19.
The incidence of obesity and type 2 diabetes mellitus have risen across the world during the past few decades and has also reached an alarming level among children. In addition, women are currently more likely than ever to enter pregnancy obese. As a result, the incidence of gestational diabetes mellitus is also on the rise. While diet and lifestyle contribute to these trends, population health data show that maternal obesity and diabetes during pregnancy during critical stages of development are major factors that contribute to the development of chronic disease in adolescent and adult offspring. Fetal programming of metabolic function, through physiological and (or) epigenetic mechanisms, may also have an intergenerational effect, and as a result may perpetuate metabolic disorders in the next generation. In this review, we summarize the existing literature that characterizes how maternal obesity and gestational diabetes mellitus contribute to metabolic and cardiovascular disorders in the offspring. In particular, we focus on animal studies that investigate the molecular mechanisms that are programmed by the gestational environment and lead to disease phenotypes in the offspring. We also review interventional studies that prevent disease with a developmental origin in the offspring.
在过去几十年间,肥胖症和2型糖尿病的发病率在全球范围内呈上升趋势,在儿童中也已达到令人担忧的水平。此外,目前女性怀孕时肥胖的可能性比以往任何时候都更高。因此,妊娠期糖尿病的发病率也在上升。虽然饮食和生活方式促成了这些趋势,但人口健康数据表明,孕期处于发育关键阶段时母亲肥胖和患糖尿病是导致青少年和成年后代患慢性病的主要因素。通过生理和(或)表观遗传机制对代谢功能进行胎儿编程,也可能产生代际效应,从而可能使下一代的代谢紊乱持续存在。在本综述中,我们总结了现有文献,这些文献描述了母亲肥胖和妊娠期糖尿病如何导致后代出现代谢和心血管疾病。我们特别关注动物研究,这些研究调查了由妊娠环境编程并导致后代出现疾病表型的分子机制。我们还综述了预防后代源于发育的疾病的干预性研究。