Pembrey Marcus, Saffery Richard, Bygren Lars Olov
School of Social & Community Medicine, University of Bristol, Bristol, UK UCL Institute of Child Health, London, UK.
Murdoch Childrens Research Institute, Parkville, Australia Department of Paediatrics, University of Melbourne, Parkville, Australia.
J Med Genet. 2014 Sep;51(9):563-72. doi: 10.1136/jmedgenet-2014-102577. Epub 2014 Jul 25.
Mammalian experiments provide clear evidence of male line transgenerational effects on health and development from paternal or ancestral early-life exposures such as diet or stress. The few human observational studies to date suggest (male line) transgenerational effects exist that cannot easily be attributed to cultural and/or genetic inheritance. Here we summarise relevant studies, drawing attention to exposure sensitive periods in early life and sex differences in transmission and offspring outcomes. Thus, variation, or changes, in the parental/ancestral environment may influence phenotypic variation for better or worse in the next generation(s), and so contribute to common, non-communicable disease risk including sex differences. We argue that life-course epidemiology should be reframed to include exposures from previous generations, keeping an open mind as to the mechanisms that transmit this information to offspring. Finally, we discuss animal experiments, including the role of epigenetic inheritance and non-coding RNAs, in terms of what lessons can be learnt for designing and interpreting human studies. This review was developed initially as a position paper by the multidisciplinary Network in Epigenetic Epidemiology to encourage transgenerational research in human cohorts.
哺乳动物实验提供了明确证据，表明父系或祖先早年暴露（如饮食或压力）会对雄性后代的健康和发育产生跨代影响。迄今为止，少数人类观察性研究表明，存在（雄性系）跨代影响，且这种影响难以简单地归因于文化和/或基因遗传。在此，我们总结相关研究，关注早年暴露的敏感时期以及传递过程和后代结果中的性别差异。因此，亲代/祖先环境中的变化可能会对下一代的表型变异产生或好或坏的影响，进而导致包括性别差异在内的常见非传染性疾病风险。我们认为，生命历程流行病学应重新构建，将上一代的暴露因素纳入其中，并对将这些信息传递给后代的机制持开放态度。最后，我们讨论动物实验，包括表观遗传遗传和非编码RNA的作用，以及从这些实验中可以汲取哪些经验教训来设计和解释人类研究。这篇综述最初是由表观遗传流行病学多学科网络撰写的立场文件，旨在鼓励在人类队列中开展跨代研究。
