Human transgenerational responses to early-life experience: potential impact on development, health and biomedical research

Marcus Pembrey, Richard Saffery, Lars Olov Bygren

Research output: Contribution to journalArticle (Academic Journal)peer-review

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Abstract

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.
Original languageEnglish
Pages (from-to)563-572
Number of pages10
JournalJournal of Medical Genetics
Volume51
Issue number9
Early online date12 Aug 2014
DOIs
Publication statusPublished - 1 Sep 2014

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