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Human transgenerational responses to early-life experience: potential impact on development, health and biomedical research
  1. Marcus Pembrey1,2,
  2. Richard Saffery3,4,
  3. Lars Olov Bygren5,6,
  4. Network in Epigenetic Epidemiology
  1. 1School of Social & Community Medicine, University of Bristol, Bristol, UK
  2. 2UCL Institute of Child Health, London, UK
  3. 3Murdoch Childrens Research Institute, Parkville, Australia
  4. 4Department of Paediatrics, University of Melbourne, Parkville, Australia
  5. 5Department of Biosciences and Rehabilitation, Karolinska Institutet, Huddinge, Sweden
  6. 6Department of Community Medicine and Rehabilitation, Umeå University, Umeå, Sweden
  1. Correspondence to Professor Marcus Pembrey, UCL Institute of Child Health, C/O 45 The Lane, West Mersea, Cochester, Essex CO5 8NR, UK; M.Pembrey{at}


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.

  • transgenerational
  • Epigenetics
  • miRNAs
  • epigenetic epidemiology
  • overkalix

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