Abstract
We review in this chapter what is known about transgenerational responses (TGRs) in humans, that is, a defined exposure in one generation producing a measurable outcome in the next, unexposed generation(s). The nature of the transgenerational signalling in humans is unknown, but epigenetic inheritance is one candidate. Human studies have focused on transmission down the male line because the Russian doll nature of the female line introduces many confounding influences that are difficult to take into account statistically. We summarise the key findings from TGR studies in three populations: ancestral food supply on grandchild’s mortality rate in Överkalix in Northern Sweden, early paternal smoking on offspring body mass index in the Avon Longitudinal Study of Parents and Children (ALSPAC) in the UK, and paternal betel quid chewing on offspring metabolic syndrome risk in Taiwan. Exposure-sensitive periods in childhood and sex-specific transmissions are features that support biological rather than cultural transmission. Drawing on the results of animal experiments, we consider some possible mechanisms, including the ‘Y dipstick’ hypothesis, by which ancestral experience might impact on the health of future generations, and how these ideas can inform the design of future studies in humans.
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Abbreviations
- ALSPAC:
-
Avon Longitudinal Study of Parents and Children
- BMI:
-
Body mass index
- TGR:
-
Transgenerational response
References
Anderson P, Kedersha N (2009) RNA granules: post-transcriptional and epigenetic modulators of gene expression. Nat Rev Mol Cell Biol 10:430–436
Anderson LM, Riffle L, Wilson R, Travlos GS, Lubomirski MS, Alvord WG (2006) Preconceptional fasting of fathers alters serum glucose in offspring of mice. Nutrition 22:327–331
Anway MD, Cupp AS, Uzumcu M, Skinner MK (2005) Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science 308:1466–1469
Anway MD, Leathers C, Skinner MK (2006) Endocrine disruptor vinclozolin induced epigenetic transgenerational adult-onset disease. Endocrinology 147:5515–5523
Barber R, Plumb MA, Boulton E, Roux I, Dubrova Y (2002) Elevated mutation rates in the germ line of first- and second-generation offspring of irradiated male mice. Proc Natl Acad Sci U S A 99:6877–6882
Boucher BJ, Ewen SW, Stowers JM (1994) Betel nut (Areca catechu) consumption and the induction of glucose intolerance in adult CD1 mice and in their F1 and F2 offspring. Diabetologia 37:49–55
Bygren LO, Kaati G, Edvinsson S (2001) Longevity determined by ancestors’ over nutrition during their slow growth period. Acta Biotheor 49:53–59
Bygren LO, Kaati G, Edvinsson S, Pembrey ME (2006) Reply to Senn. Eur J Hum Genet 14:1149–1150
Campbell JH, Perkins P (1988) Transgenerational effects of drug and hormonal treatments in mammals: a review of observations and ideas. Prog Brain Res 73:535–553
Carone BR, Fauquier L, Habib N, Shea JM, Hart CE, Li R, Bock C, Li C, Gu H, Zamore PD, Meissner A, Weng Z, Hofmann HA, Friedman N, Rando OJ (2010) Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals. Cell 143:1084–1096
Chen TH, Chiu YH, Boucher BJ (2006) Transgenerational effects of betel-quid chewing on the development of the metabolic syndrome in the Keelung Community-based Integrated Screening Program. Am J Clin Nutr 83:688–692
de Boer P, Ramos L, de Vries M, Gochhait S (2010) Memoirs of an insult: sperm as a possible source of transgenerational epimutations and genetic instability. Mol Hum Reprod 16:48–56
Drake AJ, Walker BR (2004) The intergenerational effects of fetal programming: non-genomic mechanisms for the inheritance of low birth weight and cardiovascular risk. J Endocrinol 180:1–16
Franklin TB, Russig H, Weiss IC, Gräff J, Linder N, Michalon A, Vizi S, Mansuy IM (2010) Epigenetic transmission of the impact of early stress across generations. Biol Psychiatry 68:408–415
Hara MR, Kovacs JJ, Whalen EJ, Rajagopal S, Strachan RT, Grant W, Towers AJ, Williams B, Lam CM, Xiao K, Shenoy SK, Gregory SG, Ahn S, Duckett DR, Lefkowitz RJ (2011) A stress response pathway regulates DNA damage through beta-2 adrenoreceptors and beta-arrestin-1. Nature 477:349–353
Harris A, Seckl J (2010) Glucocorticoids prenatal stress and programming of disease. Horm Behav. doi:10.1016/j.yhbeh.2010.06.007
Heijmans BT, Tobi EW, Stein AD, Putter H, Blauw GJ, Susser ES, Slagboom PE, Lumey L (2008) Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci U S A 105:17046–17049
Helgason T, Jonasson MR (1981) Evidence for a food additive as a cause of ketosis-prone diabetes. Lancet 2:716–720
Hitchins MP, Wong JJ, Suthers G, Suter CM, Martin DI, Hawkins NJ, Ward RL (2007) Inheritance of a cancer-associated MLH1 germ-line epimutation. N Engl J Med 356:697–705
Hitchins MP, Rapkins RW, Kwok CT, Srivastava S, Wong JJ, Khachigian LM, Polly P, Goldblatt J, Ward RL (2011) Dominantly inherited constitutional epigenetic silencing of MLH1 in a cancer-affected family is linked to a single nucleotide variant within the 5’UTR. Cancer Cell 20:200–213
Kaati G, Bygren LO, Edvinsson S (2002) Cardiovascular and diabetes mortality determined by nutrition during parents’ and grandparents’ slow growth period. Eur J Hum Genet 10:682–688
Kaati G, Bygren LO, Pembrey M, Sjostrom M (2007) Transgenerational response to nutrition, early life circumstances and longevity. Eur J Hum Genet 15:784–790
Kuzawa CW (2005) Fetal origins of developmental plasticity: are fetal cues reliable predictors of future nutritional environments? Am J Hum Biol 17:5–21
Lord B, Woolford L, Wang L, McDonald D, Lorimore S, Stones V, Wright E, Scott D (1998) Induction of lympho-haemopoietic malignancy: impact of preconception paternal irradiation. Int J Radiat Biol 74:721–728
Nelson VR, Nadeau JH (2010) Transgenerational genetic effects. Epigenomics 2:797–806
Nelson V, Spiezio S, Nadeau J (2010) Transgenerational genetic effects of the paternal Y chromosome on daughter’s phenotypes. Epigenomics 2:513–521
Ng SF, Lin RC, Laybutt DR, Barres R, Owens JA, Morris MJ (2010) Chronic high-fat diet in fathers programs beta-cell dysfunction in female rat offspring. Nature 467:963–966
Pembrey ME (1996) Imprinting and transgenerational modulation of gene expression; human growth as a model. Acta Genet Med Gemellol 45:111–125
Pembrey ME (2010) Male-line transgenerational responses in humans. Hum Fertil 13:268–271
Pembrey ME, Bygren LO, Kaati G, Edvinsson S, Northstone K, Sjostrom M, Golding J (2006) Sex-specific, male-line transgenerational responses in humans. Eur J Hum Genet 14:159–166
Rassoulzadegan M, Grandjean V, Gounon P, Vincent S, Gillot I, Cuzin F (2006) RNA-mediated non-mendelian inheritance of an epigenetic change in the mouse. Nature 441:469–474
Tobi EW, Lumey LH, Talens RP, Kremer D, Putter H, Stein AD, Slagboom PE, Heijmans BT (2009) DNA methylation differences after exposure to prenatal famine are common and timing- and sex-specific. Hum Mol Genet 18:4046–4053
Wilkin TJ, Voss LD (2004) Metabolic syndrome: maladaptation to a modern world. J R Soc Med 97:511–520
Yazbek SN, Spiezio SH, Nadeau JH, Buchner DA (2010) Ancestral paternal genotype controls body weight and food intake for multiple generations. Hum Mol Genet 19:4134–4144
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Pembrey, M.E., Bygren, L.O., Golding, J. (2013). The Nature of Human Transgenerational Responses. In: Jirtle, R., Tyson, F. (eds) Environmental Epigenomics in Health and Disease. Epigenetics and Human Health. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-23380-7_12
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DOI: https://doi.org/10.1007/978-3-642-23380-7_12
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