Free Standard AU & NZ Shipping For All Book Orders Over $80!
Register      Login
Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
RESEARCH ARTICLE

Long-term effects of nutritional programming of the embryo and fetus: mechanisms and critical windows

Michael E. Symonds A B , Terence Stephenson A , David S. Gardner A and Helen Budge A
+ Author Affiliations
- Author Affiliations

A Centre for Reproduction and Early Life, Institute of Clinical Research, University Hospital, Nottingham, NG7 2UH, UK.

B Corresponding author. Email: michael.symonds@nottingham.ac.uk

Reproduction, Fertility and Development 19(1) 53-63 https://doi.org/10.1071/RD06130
Published: 12 December 2006

Abstract

The maternal nutritional and metabolic environment is critical in determining not only reproduction, but also long-term health and viability. In the present review, the effects of maternal nutritional manipulation at defined stages of gestation coinciding with embryogenesis, maximal placental or fetal growth will be discussed. Long-term outcomes from these three developmental windows appear to be very different, with brain and cardiovascular function being most sensitive to influences in the embryonic period, the kidney during placental development and adipose tissue in the fetal phase. In view of the similarities in fetal development, number and maturity at birth, there are close similarities in these outcomes between findings from epidemiological studies in historical human cohorts and nutritional manipulation of large animals, such as sheep. One key nutrient that may modulate the long-term metabolic effects is the supply of glucose from the mother to the fetus, because this is sensitive to both global changes in food intake, maternal glucocorticoid status and an increase in the carbohydrate content of the diet. The extent to which these dietary-induced changes may reflect epigenetic changes remains to be established, especially when considering the very artificial diets used to induce these types of effects. In summary, the maintenance of a balanced and appropriate supply of glucose from the mother to the fetus may be pivotal in ensuring optimal embryonic, placental and fetal growth. Increased or decreased maternal plasma glucose alone, or in conjunction with other macro- or micronutrients, may result in offspring at increased risk of adult diseases.

Extra keywords: adipose tissue, blood pressure, cortisol, kidney.


Acknowledgments

The authors acknowledge the support of the British Heart Foundation and the European Union Sixth Framework Programme for Research and Technical Development of the European Community-The Early Nutrition Programming Project (FOOD-CT-2005-007036) in their research.


References

Armitage, J. A. , Khan, I. Y. , Taylor, P. D. , Nathanielsz, P. W. , and Poston, L. (2004). Developmental programming of the metabolic syndrome by maternal nutritional imbalance: how strong is the evidence from experimental models in mammals? J. Physiol. 561, 355–377.
Crossref | GoogleScholarGoogle Scholar | PubMed | Budge H., and Symonds M. E. (2006). Fetal and neonatal nutrition: lipid and carbohydrate requirements and adaptations to altered supply at birth. In ‘The Textbook of Perinatal Medicine’. (Eds H. N. Winn and P. D. Gluckman.) pp. 1007–1016. (Taylor & Francis: Great Yarmouth.)

Budge, H. , Bispham, J. , Dandrea, J. , Evans, E. , and Heasman, L. , et al. (2000). Effect of maternal nutrition on brown adipose tissue and prolactin receptor status in the fetal lamb. Pediatr. Res. 47, 781–786.
PubMed | Cannon B., Connoley E., Obregon M.-J., and Nedergaard J. (1988). Perinatal activation of brown adipose tissue. In ‘The Endocrine Control of the Fetus’. (Eds W. Kunzel and A. Jesen.) pp. 306–320. (Springer Verlag: Berlin.)

Carter, A. M. , and Mess, A. (2006). Evolution of the placenta in Eutherian mammals. Placenta ,in press.
Finn C. A. (1994). Implantation. In ‘Marshall’s Physiology of Reproduction, 4th edn, Volume 3, Pregnancy and Lactation, Part Two Fetal Physiology, Parturition and Lactation’. (Ed. G. E. Lamming.) pp. 159–234. (Chapman & Hall: London.)

Finn, D. , Lomax, M. A. , and Trayhurn, P. (1998). An immunohistochemical and in situ hybridisation study of the postnatal development of uncoupling protein-1 and uncoupling protein-1 mRNA in lamb perirenal adipose tissue. Cell Tissue Res. 294, 461–466.
Crossref | GoogleScholarGoogle Scholar | PubMed | Symonds M. E., and Gardner D. S. (2006). Development of obesity. In ‘Developmental Origins of Health and Disease’. (Eds P. D. Gluckman and M. A. Hanson.) pp. 397–403. (Cambridge University Press: Cambridge.)

Symonds, M. E. , Bryant, M. J. , and Lomax, M. A. (1986). The effect of shearing on the energy metabolism of the pregnant ewe. Br. J. Nutr. 56, 635–643.
Crossref | GoogleScholarGoogle Scholar | PubMed | Symonds M. E., Budge H., and Stephenson T. (2003a). Physiological and nutritional aspects of the placenta. In ‘Nutritional in Early Life: Concepts and Practice’. (Eds J. B. Morgan and J. W. T. Dickerson.) pp. 91–121. (Wiley & Sons: Chichester.)

Symonds, M. E. , Mostyn, A. , Pearce, S. , Budge, H. , and Stephenson, T. (2003b). Endocrine and nutritional regulation of fetal adipose tissue development. J. Endocrinol. 179, 293–299.
Crossref | GoogleScholarGoogle Scholar | PubMed | Symonds M. E., Gardner D. S., Pearce S., and Stephenson T. (2004a). Endocrine responses to fetal undernutrition: the growth hormone (GH): insulin-like growth factor (IGF) axis. In ‘Fetal Nutrition and Adult Disease: Programming of Chronic Disease Through Fetal Exposure to Undernutrition’. (Ed. S. C. Langley-Evans.) pp. 353–380. (CAB International: Oxford.)

Symonds, M. E. , Pearce, S. , Bispham, J. , Gardner, D. S. , and Stephenson, T. (2004b). Timing of nutrient restriction and programming of fetal adipose tissue development. Proc. Nutr. Soc. 63, 397–403.
Crossref | GoogleScholarGoogle Scholar | PubMed | Symonds M. E., Budge H., Mostyn A., Stephenson T., and Gardner D. S. (2007). Maternal diet through pregnancy: the key to future good health of the next generation? In ‘Reducing Diets: New Research’. (Ed. F. Columbus.) In press. (Nova Science Publishers: New York.)

Thompson, G. E. , Bassett, J. M. , Samson, D. E. , and Slee, J. (1982). The effect of cold exposure of pregnant sheep on fetal plasma nutrients, hormones and birth weight. Br. J. Nutr. 48, 59–64.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Vickers, M. H. , Breier, B. H. , McCarthy, D. , and Gluckman, P. D. (2003). Sedentary behavior during postnatal life is determined by the prenatal environment and exacerbated by postnatal hypercaloric nutrition. Am. J. Physiol. Regul. Intergr. Comp. Physiol. 285, R271–R273.


Warnes, K. , Morris, M. J. , Symonds, M. E. , Phillips, I. D. , Owens, J. A. , and McMillen, I. C. (1998). Effects of gestation, cortisol and maternal undernutrition on hypothalamic neuropeptide Y mRNA levels in the sheep fetus. J. Neuroendocrinol. 10, 51–57.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Waterland, R. A. , and Jirtle, R. L. (2003). Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol. Cell. Biol. 23, 5293–5300.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Waterland, R. A. , Lin, J. R. , Smith, C. A. , and Jirtle, R. L. (2006). Post-weaning diet affects genomic imprinting at the insulin-like growth factor 2 (Igf2) locus. Hum. Mol. Genet. 15, 705–716.
Crossref | GoogleScholarGoogle Scholar | PubMed |

White, B. D. , Dean, R. G. , and Martin, R. J. (1994). Short-term dexamethasone treatment increases food intake, but apparently not through changes in NPY content in the PVN. Ann. N.Y. Acad. Sci. 739, 339–340.
PubMed |

Whorwood, C. B. , Firth, K. M. , Budge, H. , and Symonds, M. E. (2001). Maternal undernutrition during early- to mid-gestation programmes tissue-specific alterations in the expression of the glucocorticoid receptor, 11β-hydroxysteroid dehydrogenase isoforms and type 1 angiotensin II receptor in neonatal sheep. Endocrinology 142, 2854–2864.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Widdowson, E. M. (1950). Chemical composition of newly born animals. Nature 166, 626–628.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Wintour, E. M. , and Moritz, K. M. (1997). Comparative aspects of fetal renal development. Equine Vet. J. 24, 51–58.


Wintour, E. M. , Alcorn, D. , McFarlane, A. , Moritz, K. , Potocnik, S. J. , and Tangalakis, K. (1994). Effect of maternal glucocorticoid treatment on fetal fluids in sheep at 0.4 gestation. Am. J. Physiol. 266, R1174–R1181.
PubMed |

Woods, L. L. (2006). Maternal glucocorticoids and prenatal programming of hypertension. Am. J. Physiol. Regul. Intergr. Comp. Physiol. 291, R1069–R1075.


Woods, L. L. , and Weeks, D. A. (2005). Prenatal programming of adult blood pressure: role of maternal corticosteroids. Am. J. Physiol. Regul. Intergr. Comp. Physiol. 289, R955–R962.


Woods, L. L. , Ingelfinger, J. R. , Nyengaard, J. R. , and Rasch, R. (2001). Maternal protein restriction suppresses the newborn renin-angiotensin system and programs adult hypertension in rats. Pediatr. Res. 49, 460–467.
PubMed |

Young, L. E. , Fernandes, K. , McEvoy, T. G. , Butterwith, S. C. , and Gutierrez, C. G. , et al. (2001). Epigenetic change in IGF2R is associated with fetal overgrowth after embryo culture. Nat. Genet. 27, 153–154.
Crossref | GoogleScholarGoogle Scholar | PubMed |