Biological Theory

, Volume 6, Issue 1, pp 65–72 | Cite as

Expanding the Temporal Dimensions of Developmental Biology: The Role of Environmental Agents in Establishing Adult-Onset Phenotypes

  • Scott F. GilbertEmail author
Original Paper


Developmental biology is expanding into several new areas. One new area of study concerns the production of adult-onset phenotypes by exposure of the fetus or neonate to environmental agents. These agents include maternal nutrients, developmental modulators (endocrine disruptors), and maternal care. In all three cases, a major mechanism for the generation of the altered phenotype is chromatin modification. Nutrient conditions, developmental modulators, and even maternal care appear to alter DNA methylation and other associated changes in chromatin that regulate gene expression. This brings a new, under-appreciated, dimension of gene regulation into developmental biology, and it also demonstrates the poverty of the nature versus nurture framework for discussing phenotype production. Moreover, while such epigenetic mechanisms undermine genetic determinism, they add a layer of probabilistic biological causality for the maintenance of social inequalities.


Behavior Development Developmental origins of adult disease Environmental causation Epigenetic Nature–nurture Nutrition Plasticity 


  1. Anway MD, Cupp AS, Uzumcu M, Skinner MK (2005) Epigenetic transgenerational actions of endocrine disruptors and mate fertility. Science 308:1466–1469CrossRefGoogle Scholar
  2. Anway MD, Memon MA, Uzumcu M, Skinner MK (2006) Transgenerational effect of the endocrine disruptor vinclozolin on male spermatogenesis. J Androl 27:868–879CrossRefGoogle Scholar
  3. Beldade P, Mateus AR, Keller RA (2011) Evolution and molecular mechanisms of adaptive developmental plasticity. Mol Ecol 20:1347–1363CrossRefGoogle Scholar
  4. Bromer JG, Zhou Y, Taylor MB, Doherty L, Taylor HS (2010) Bisphenol-A exposure in utero leads to epigenetic alterations in the developmental programming of uterine estrogen response. FASEB J 24(7): 2273–2280Google Scholar
  5. Burdge GC, Hanson MA, Slater-Jefferies JL, Lillycrop KA (2007a) Epigenetic regulation of transcription: a mechanism for inducing variations in phenotype (fetal programming) by differences in nutrition during early life? Br J Nutr 97:1036–1046CrossRefGoogle Scholar
  6. Burdge GC, Slater-Jefferies J, Torrens C, Phillips ES, Hanson MA, Lillycrop KA (2007b) Dietary protein restriction of pregnant rats in the F0 generation induces altered methylation of hepatic gene promoters in the adult male offspring in the F1 and F2 generations. Br J Nutr 97:435–439CrossRefGoogle Scholar
  7. Cameron NM, Shahrokh D, Del Corpo A, Dhir SK, Szyf M, Champagne FA, Meaney MJ (2008) Epigenetic programming of phenotypic variations in reproductive strategies in the rat through maternal care. J Neuroendocrinol 20:795–801CrossRefGoogle Scholar
  8. Champagne FA (2008) Epigenetic mechanisms and the transgenerational effects of maternal care. Front Neuroendocrinol 29:386–397CrossRefGoogle Scholar
  9. Champagne FA, Meaney MJ (2007) Transgenerational effects of social environment on variations in maternal care and behavioral response to novelty. Behav Neurosci 121:1353–1363CrossRefGoogle Scholar
  10. Champagne FA, Weaver IC, Diorio J, Dymov S, Szyf M, Meaney MJ (2006) Maternal care associated with methylation of the estrogen receptor-alpha1b promoter and estrogen receptor-alpha expression in the medial preoptic area of female offspring. Endocrinology 147:2909–2915CrossRefGoogle Scholar
  11. Cubas P, Vincent C, Coen E (1999) An epigenetic mutation responsible for natural variation in floral symmetry. Nature 401:157–161CrossRefGoogle Scholar
  12. Dolinoy DC, Huang D, Jirtle RL (2007) Maternal nutrient supplementation counteracts bisphenol A-induced DNA hypomethylation in early development. Proc Natl Acad Sci USA 104:13056–13061CrossRefGoogle Scholar
  13. Durando M, Kass L, Piva J, Sonnenschein C, Soto AM, Luque EH, Muñz-de-Toro M (2007) Prenatal bisphenol A exposure induces preneoplastic lesions in the mammary gland in Wistar rats. Environ Health Perspect 115:80–86CrossRefGoogle Scholar
  14. Flegal KM, Carroll MD, Ogden CL, Curtin LR (2010) Prevalence and trends in obesity among US adults, 1999–2008. J Am Med Assoc 303:235–241CrossRefGoogle Scholar
  15. Gilbert SF (2002) The genome in its ecological context: philosophical perspectives on interspecies epigenesis. Ann N Y Acad Sci 981:202–218CrossRefGoogle Scholar
  16. Gilbert SF (2010) Developmental biology, 9th edn. Sinauer Associates, SunderlandGoogle Scholar
  17. Gilbert SF (2012) Developmental biology: Interpreting developmental signals. In: Kull K, Hofmeyer J (eds) Approaches to the Semiosis of Evolution (in press)Google Scholar
  18. Gilbert SF, Epel D (2009) Ecological developmental biology. Sinauer Associates, SunderlandGoogle Scholar
  19. Gluckman PD, Hanson MA (2004) Living with the past: evolution, development, and patterns of disease. Science 305:1733–1736CrossRefGoogle Scholar
  20. Gluckman PD, Hanson MA (2007) Mismatch: why our world no longer fits our bodies. Oxford University Press, OxfordGoogle Scholar
  21. Godfrey KM, Sheppard A, Gluckman PD, Lillycrop KA, Burdge GC, McLean C, Rodford J, Slater-Jefferies JL, Garratt E, Crozier SR, Emerald BS, Gale CR, Inskip HM, Cooper C, Hanson MA (2011) Epigenetic gene promoter methylation at birth is associated with child’s later adiposity. Diabetes 60:1528–1534CrossRefGoogle Scholar
  22. Gould SJ (1985) Living with connections. In: The Flamingo’s Smile, Norton, New York, pp 64–77Google Scholar
  23. Grün F, Watanabe H, Zamanian Z, Maeda L, Arima K, Cubacha R, Gardiner DM, Kanno J, Iguchi T, Blumberg B (2006) Endocrine-disrupting organotin compounds are potent inducers of adipogenesis in vertebrates. Mol Endocrinol 20:2141–2155CrossRefGoogle Scholar
  24. Guerrero-Bosagna C, Settles M, Lucker B, Skinner MK (2010) Epigenetic transgenerational actions of vinclozolin on promoter regions of the sperm epigenome. PLoS One 5(9)Google Scholar
  25. Hales CN, Barker DJ (1992) Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Diabetologia 35:595–601CrossRefGoogle Scholar
  26. Hales CN, Barker DJ (2001) The thrifty phenotype hypothesis. Br Med Bull 60:5–20CrossRefGoogle Scholar
  27. Ho S-M, Tang W-Y, Belmonte de Frausto J, Prins GS (2006) Developmental exposure to estradiol and bisphenol A increases susceptibility to prostate carcinogenesis and epigenetically regulates phosphodiesterase type 4 variant 4. Cancer Res 66:5624–5632CrossRefGoogle Scholar
  28. Hoverman JT, Relyea RA (2007) The rules of engagement: how to defend against combinations of predators. Oecologia 154:551–560CrossRefGoogle Scholar
  29. Jablonka E, Raz G (2009) Transgenerational epigenetic inheritance: prevalence, mechanisms, and implications for the study of heredity and evolution. Q Rev Biol 84:131–176CrossRefGoogle Scholar
  30. Janesick A, Blumberg B (2011a) Minireview: PPARγ as the target of obesogens. J Stero Biochem Mol Biol 27:4–8CrossRefGoogle Scholar
  31. Janesick A, Blumberg B (2011b) Endocrine disrupting chemicals and the developmental programming of adipogenesis and obesity. Birth Defects Res C Embryo Today 93:34–50CrossRefGoogle Scholar
  32. Kaati G, Bygren LO, Pembrey M, Sjostrom M (2007) Transgenerational response to nutrition, early life circumstances and longevity. Eur J Hum Genet 15:784–790CrossRefGoogle Scholar
  33. Kirchner S, Kieu T, Chow C, Casey S, Blumberg B (2010) Prenatal exposure to the environmental obesogen tributyltin predisposes multipotent stem cells to become adipocytes. Mol Endocrinol 24:526–539CrossRefGoogle Scholar
  34. Kundakovic M, Champagne FA (2011) Epigenetic perspective on the developmental effects of bisphenol-A. Brain Behav Immun 25:1084–1093CrossRefGoogle Scholar
  35. Landrigan PJ, Rauh VA, Galvez MP (2010) Environmental justice and the health of children. Mt Sinai J Med 77:178–187CrossRefGoogle Scholar
  36. Laplane L (2011) Stem cells and the temporal boundaries of development: Toward a species-dependent view. Biol Theory. doi: 10.1007/s13752-011-0009-z
  37. Lederberg J (1966) Remarks. In: Monroy A, Moscona AA (eds) Current Topics in Developmental Biology. Academic press, New York, p ix–xiiiGoogle Scholar
  38. Lillycrop KA, Phillips ES, Jackson AA, Hanson MA, Burdge GC (2005) Dietary protein restriction of pregnant rats induces and folic acid supplementation prevents epigenetic modification of hepatic gene expression in the offspring. J Nutr 135:1382–1386Google Scholar
  39. Lillycrop KA, Rodford J, Garratt ES, Slater-Jefferies JL, Godfrey KM, Gluckman PD, Hanson MA, Burdge GC (2010) Maternal protein restriction with or without folic acid supplementation during pregnancy alters the hepatic transcriptome in adult male rats. Br J Nutr 103:1711–1719CrossRefGoogle Scholar
  40. Martinez-Hernandez A, Enriquez L, Moreno–Moreno MJ, Marti A (2007) Genetics of obesity. Public Health Nutr 10:1138–1144CrossRefGoogle Scholar
  41. Mazmanian S (2010) Has the microbiota played a critical role in the evolution of the adaptive immune system? Science 330:1768–1773CrossRefGoogle Scholar
  42. McFall-Ngai MJ (2002) Unseen forces: the influence of bacteria on animal development. Dev Biol 242:1–14CrossRefGoogle Scholar
  43. McGowan PO, Sasaki A, D’Alessio AC, Dymov S, Labonté B, Szyf M, Turecki G, Meaney MJ (2009) Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat Neurosci 12:342–348CrossRefGoogle Scholar
  44. Miyakawa H, Imai M, Sugimoto N, Ishikawa Y, Ishikawa A, Ishigaki H, Okada Y, Miyazaki S, Koshikawa S, Cornette R, Miura T (2010) Gene up-regulation in response to predator kairomones in the water flea, Daphnia pulex. BMC Dev Biol 10:45CrossRefGoogle Scholar
  45. Morange M (2011) Development and aging. Biol Theory. doi: 10.1007/s13752-011-0010-6
  46. Moscona AA, Monroy A (eds) (1966) Current topics in developmental biology, Vol 1. Academic Press, New YorkGoogle Scholar
  47. Myers JP, Zoeller RT, vom Saal FS (2009) A clash of old and new scientific concepts in toxicity, with important implications for public health. Environ Health Perspect 117:1652–1655Google Scholar
  48. Nicoglou A (2011) Defining the boundaries of development with plasticity. Biol Theory. doi: 10.1007/s13752-011-0003-5
  49. Oberdörster E, McClellan-Green P (2002) Mechanisms of imposex induction in the mud snail, Ilyanassa obsoleta: TBT as a neurotoxin and aromatase inhibitor. Mar Environ Res 54:715–718CrossRefGoogle Scholar
  50. Pembrey ME (2010) Male-line transgenerational responses in humans. Human Fertility 13:268–271CrossRefGoogle Scholar
  51. Pradeu T (2011). A mixed self: The role of symbiosis in development. Biol Theory. doi: 10.1007/s13752-011-0011-5
  52. Relyea RA, Hoverman JT (2003) The impact of predators and competitors on the morphology and fitness of juvenile treefrogs. Oecologia 134:596–604Google Scholar
  53. Rosenberg E, Sharon G, Zilber-Rosenberg I (2009) The hologenome theory of evolution: a fusion of neo-Darwinism and Lamarckism. Environ Microbiol 11:2959–2962CrossRefGoogle Scholar
  54. Saffo MB (2006) Symbiosis: the way of all life. In: Seckbach J (ed) Life as we know it. Springer, New York, pp 325–339Google Scholar
  55. Skinner MK, Manikkam M, Guerrero-Bosagna C (2010) Epigenetic transgenerational actions of environmental factors in disease etymology. Trends Endocrinol Metab 21:214–222CrossRefGoogle Scholar
  56. Soto AM, Sonnenschein C (2010) Environmental causes of cancer: Endocrine disruptors as carcinogens. Nat Rev Endocrinol 6:363–370CrossRefGoogle Scholar
  57. Su JG, Jerrett M, de Nazelle A, Wolch J (2011) Does exposure to air pollution in urban parks have socioeconomic, racial or ethnic gradients? Environ Res 111:319–328CrossRefGoogle Scholar
  58. Sun J (2010) Enteric bacteria and cancer stem cells. Cancers 3:285–297CrossRefGoogle Scholar
  59. Vandenberg LN, Maffini MV, Schaeberle CM, Ucci AA, Sonnenschein C, Rubin BS, Soto AM (2008) Perinatal exposure to the xenoestrogen bisphenol-A induces mammary intraductal hyperplasias in adult CD-1 mice. Reprod Toxicol 26:210–219CrossRefGoogle Scholar
  60. Vermorel M, Lazzer S, Bitar A, Ribeyre J, Montaurier C, Fellmann N, Coudert J, Meyer M, Boirie Y (2005) Contributing factors and variability of energy expenditure in non-obese, obese, and post-obese adolescents. Reprod Nutr Dev 45:129–142CrossRefGoogle Scholar
  61. Vom Saal F et al (2007) Chapel Hill bispenol-A expert panel consensus statement: integration of mechanisms, effects in animals, and potential to impact human public heath at current levels of exposure. Reprod Toxocol 24:131–138 thirty-five othersCrossRefGoogle Scholar
  62. Voog J, Jones DL (2010) Stem cells and the niche: a dynamic duo. Cell Stem Cell 6:103–115CrossRefGoogle Scholar
  63. Wadia PR, Vandenberg LN, Schaeberle CM, Rubin BS, Sonnenschein C, Soto AM (2007) Perinatal bisphenol A exposure increases estrogen sensitivity of the mammary gland in diverse mouse strains. Environ Health Perspect 115:592–598CrossRefGoogle Scholar
  64. Walker DM, Gore AC (2011) Transgenerational neuroendocrine disruption of reproduction. Nat Rev Endocrinol 7:197–207CrossRefGoogle Scholar
  65. Wallace I, Wallace A (1979) The Two. Bantam Books, New YorkGoogle Scholar
  66. Weaver IC (2007) Epigenetic programming by maternal behavior and pharmacological intervention. Nature versus nurture: let’s call the whole thing off. Epigenetics 2:22–28CrossRefGoogle Scholar
  67. Weaver IC, Cervoni N, Champagne FA, D’Alessio AC, Sharma S, Seckl JR, Dymov S, Szyf M, Meaney MJ (2004) Epigenetic programming by maternal behavior. Nat Neurosci 7:847–854CrossRefGoogle Scholar
  68. Weiss PA (ed) (1956) The developmental biology conference series. University of Chicago Press, ChicagoGoogle Scholar
  69. Weiss PA (ed) (1959) Developmental biology. Academic Press, New YorkGoogle Scholar

Copyright information

© Konrad Lorenz Institute 2011

Authors and Affiliations

  1. 1.Department of BiologySwarthmore CollegeSwarthmoreUSA
  2. 2.Biotechnology InstituteUniversity of HelsinkiHelsinkiFinland

Personalised recommendations